Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, yet their role in anoxia-induced transcriptomic changes in crucian carp () - a species that endures months without oxygen at low temperatures - remains...Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, yet their role in anoxia-induced transcriptomic changes in crucian carp () - a species that endures months without oxygen at low temperatures - remains unclear. Because existing genome annotations focus on protein-coding genes, we aimed to annotate lncRNAs in crucian carp, assess their potential for involvement in mRNA regulation during anoxia and reoxygenation, and characterize differentially regulated lncRNAs and nearby putative interaction partners (IPs). Using next-generation RNA sequencing of the brain across normoxia, anoxia, and reoxygenation ( = 10 per group), we assembled 145,264 transcripts with a reference-guided approach. With CPC2, CNCI, CPAT, and FEELnc, we identified 6072 lncRNAs. Anoxia elicited a robust transcriptomic response: 56,440 transcripts were differentially expressed (adjusted -value < 0.05; |log2(fold change)| > 0.38), including 1321 lncRNAs. FEELnc classification highlighted proximal RNA transcripts suggestive of cis-acting lncRNA functions. Most (60%) DElncRNA - IP interaction sites were intergenic, predominantly on the same strand within intergenic subtypes, with many features nested within genic contexts. Notably, log2-fold changes in RNA abundance of predicted DE IPs positively correlated with those of their corresponding DElncRNAs. These results provide a comprehensive lncRNA annotation for crucian carp and reveal extensive lncRNA co-expression with nearby genes during anoxia and reoxygenation, supporting a potential cis-regulatory role in the adaptive transcriptomic response to oxygen deprivation.
Co-translational mRNA decay occurs when 5'to3' exonucleases follow the last translating ribosome, generating ribosome protected fragments. Degradome sequencing (5PSeq)therefore offers unique insights into ribosome dynam...Co-translational mRNA decay occurs when 5'to3' exonucleases follow the last translating ribosome, generating ribosome protected fragments. Degradome sequencing (5PSeq)therefore offers unique insights into ribosome dynamics. Despite its potential, resources for systematic analysis of 5'P mRNA decay intermediates and associated features, such as ribosome stalls and collisions, are scarce. We introduce 5PSeq Explorer, a web-based platform built from 773 uniformly processed 5PSeq datasets across 23 species in bacteria and Ascomycota suitable for exploring ribosome dynamics in vivo at codon, amino acid, and transcript levels. By integrating normalized counts, structured metadata, and scalable visualization tools, 5PSeq Explorer provides a framework for studying the crosstalk between mRNA decay and ribosome dynamics. To ensure reproducibility and accessibility, we offer both a public web interface and a Docker-based plug-and-play local version. URL: https://fivepseq-explorer.serve.scilifelab.se/app/fivepseq-explorer.
Human papillomaviruses (HPVs) cause diverse cutaneous and mucosal diseases, with several genotypes strongly associated with cervical cancer. Beyond the well-established role of cellular microRNAs (miRNAs) in gene regulat...Human papillomaviruses (HPVs) cause diverse cutaneous and mucosal diseases, with several genotypes strongly associated with cervical cancer. Beyond the well-established role of cellular microRNAs (miRNAs) in gene regulation, increasing evidence shows that HPV also encodes its own viral miRNAs (v-miRNAs). These v-miRNAs modulate both viral and host gene expression, influencing key pathways involved in oncogenesis, including cell cycle control, apoptosis, immune evasion, and epithelial - mesenchymal transition. By shaping these regulatory networks, HPV-derived miRNAs promote viral persistence and contribute to malignant transformation. Their stability and specificity also make them promising biomarkers for cervical cancer diagnosis and prognosis, although clinical translation remains challenging. This review provides an updated overview of HPV-encoded miRNAs, their validated molecular targets, and their roles in tumour development. It also highlights emerging therapeutic strategies and future perspectives for integrating miRNA-based approaches into precision oncology for HPV-related cervical cancer.
MicroRNAs (miRNAs) are small, non-coding RNA molecules that act as essential post-transcriptional regulators in various biological processes. Many studies suggest that miRNAs may modulate the host's immune response or ev...MicroRNAs (miRNAs) are small, non-coding RNA molecules that act as essential post-transcriptional regulators in various biological processes. Many studies suggest that miRNAs may modulate the host's immune response or even viral replication during infection. We have identified hsa-miR-203a-3p as a key regulatory candidate influencing innate immune responses, based on a comprehensive analysis of publicly available transcriptomic datasets involving H7N9, HCV, or DENV2 infection. Pathway enrichment analysis of microRNA-targeted genes reveals that hsa-miR-203a-3p targets several components of type I interferon signalling and JAK-STAT pathway. In this study, we report a novel role of hsa-miR-203a-3p as it is elevated in response to polyinosinic-polycytidylic acid [poly(I:C)] transfection and infection with RNA viruses Newcastle Disease Virus (NDV) and A/PR8/H1N1 influenza virus. We found that hsa-miR-203a-3p promotes the A/PR8/H1N1 virus replication by suppressing the host's type-I interferons and interferon-stimulated genes. Our investigation demonstrated that overexpression of hsa-miR-203a-3p led to reduced expression of interferon stimulated genes (ISGs). This regulation is likely mediated through the direct binding of hsa-miR-203a-3p to the 3' UTRs of Janus-activated kinase 1 (JAK1), STAT1 and several IFN-α transcripts. Collectively, these findings highlight the pivotal role of hsa-miR-203a-3p in immune homoeostasis; it regulates type I IFN signalling and downstream antiviral responses, thereby facilitating A/PR8/H1N1 and NDV infection.
Alzheimer's disease (AD) is a typical neurodegenerative disorder, characterized by the deposition of β-amyloid (Aβ) plaques. β- and γ-secretases generate Aβ by cleaving amyloid precursor protein. The imbalance between it...Alzheimer's disease (AD) is a typical neurodegenerative disorder, characterized by the deposition of β-amyloid (Aβ) plaques. β- and γ-secretases generate Aβ by cleaving amyloid precursor protein. The imbalance between its production and clearance leads to Aβ accumulation, causing neuronal damage through mechanisms such as inducing oxidative stress and inflammatory responses. Long non-coding RNAs (LncRNAs), composed of more than 200 nucleotides, usually do not encode proteins and are involved in processes such as gene expression regulation, chromatin remodelling, and cell cycle control. Studies have shown that LncRNAs play a key role in brain development and the maintenance of neuronal function, especially by influencing Aβ deposition to affect the progression of AD. This review summarizes the pathways by which LncRNAs affect Aβ deposition, classifies them according to their modes of action, discusses the existing problems in current research, and summarizes and prospects their role in the treatment of AD.
Exploring the role of key genes in colorectal cancer (CRC) progression to identify effective targets is highly practical. Previous studies have shown that miR-1276/ACTB plays an important regulatory role in CRC. In addit...Exploring the role of key genes in colorectal cancer (CRC) progression to identify effective targets is highly practical. Previous studies have shown that miR-1276/ACTB plays an important regulatory role in CRC. In addition to miRNA, lncRNA also play a crucial role in tumour progression. However, there are currently no studies exploring the relationship between lncRNAs and miR-1276/LACTB. Analysis of the relationship between lncRNAs and miR-1276 using ENCORI database showed that lncRNA-LINC00852 bound to miR-1276 and inhibited its expression, thereby promoting LACTB expression, and miR-1276 upregulation weakened the ability of LINC00852 to promote LACTB expression. ENCORI and TCGA data also indicated that the expression of LINC00852 and LACTB in CRC was significantly downregulated, while miR-1276 expression was significantly upregulated. LINC00852 overexpression promoted E-cadherin expression, increased the activities of Caspase-3/8/9 and PARP, inhibited the expression of N-cadherin and Vimentin, and decreased the expression and secretion of MMP-2 and MMP-9. LINC00852 inhibited CRC cell viability, invasion and migration while promoting apoptosis. miR-1276 overexpression or LACTB knockdown significantly blocked the regulatory effect of LINC00852 on CRC cell biological function. Further xenograft mouse model confirmed that LINC00852 downregulated miR-1276 expression, enhanced the expression of LACTB and FDX1, increased tumour copper levels and inhibited tumour formation, indicating that the anticancer effect of LINC00852/LACTB may also be related to cuproptosis. However, LACTB knockdown blocked the inhibitory effect of LINC00852 on tumour formation. Therefore, LINC00852 inhibits CRC progression through miR-1276/LACTB, indicating that LINC00852/miR-1276/LACTB axis is an important pathway closely related to the occurrence and development of CRC.
Poly(UG) repeats or pUG RNAs can fold into a left-handed parallel quadruplex, the pUG fold. The pUG fold directs the epigenetic amplification of RNAi in elegans, and pUG sequences are abundant in eukaryotic transcriptom...Poly(UG) repeats or pUG RNAs can fold into a left-handed parallel quadruplex, the pUG fold. The pUG fold directs the epigenetic amplification of RNAi in elegans, and pUG sequences are abundant in eukaryotic transcriptomes. Here, we report the sequence and ionic requirements for pUG folding. The pUG fold preferentially incorporates 12 guanosines but has an otherwise flexible sequence requirement. The uridines can be substituted with other nucleotides, with some sequence variants folding better than pUG RNA. The GA repeat sequence (GA) also forms a pUG-like fold, albeit with lower thermodynamic stability than (GU). The pUG fold can tolerate multiple deoxyribose substitutions but does not fold when the backbone is entirely deoxyribose. It has a high affinity and specificity for potassium ions ( = 6 mM) and does not fold in sodium or ammonium. Addition of 2 mM Mg does not further stabilize the pUG fold, and the polyamines spermine and spermidine do not affect its stability. Finally, the pUG fold is sensitive to surrounding sequence context and complementary flanking sequences can stabilize pUG folds, while other sequences can interfere with folding. These data provide an improved ability to understand and predict pUG folds.
Despite growing interest in profiling microRNAs (miRNAs) in infant and toddler stool, no studies have compared protocols for preserving and extracting miRNAs from this specimen type. Three commercially available kits and...Despite growing interest in profiling microRNAs (miRNAs) in infant and toddler stool, no studies have compared protocols for preserving and extracting miRNAs from this specimen type. Three commercially available kits and four preservation methods were compared for their ability to yield high quality RNA from children <2 years of age (infant/toddler). Of the three RNA extraction kits compared, Zymo BIOMICs yielded the highest RNA Quality Number (RQN) (median (range) RQN 9.4 (5.7-10.0)). Of the four preservation methods tested, RNAlater and Zymo DNA/RNA Shield Faecal Collection Tubes yielded the highest two RQNs (median (range) RQN 9.8 (5.7-10.0) and 9.4 (5.4-10.0), respectively), which did not differ from each other ( = 0.47). Subsequently, miRNA-seq was used to compare miRNA profiles for RNA extracted using the Zymo BIOMICs kit from paired aliquots of the same stool sample ( = 4 infant donors) collected into RNAlater and Zymo DNA/RNA Shield Faecal Collection Tubes. The percentage of reads classified as human and the percentage of human reads aligning to miRBase did not differ for samples collected in RNAlater versus Zymo Shield ( = 0.12 and = 0.86, respectively). Furthermore, after multiple testing correction, normalized miRNA counts did not differ between the two preservatives for any of the 42 human miRNAs detected across the eight samples (p ≥ 0.05). Collecting stool from infants and toddlers <2 years of age in either RNAlater or Zymo DNA/RNA Shield Faecal Collection Tubes, when paired with RNA extraction using the Zymo BIOMICs extraction kit, yielded high-quality RNA with similar human miRNA profiles.
Type III CRISPR systems are defined by the presence of the Cas10 protein and are among the most abundant CRISPR systems in nature. Cas10 forms a complex with crRNA and several Cas proteins that surveils prokaryotic cells...Type III CRISPR systems are defined by the presence of the Cas10 protein and are among the most abundant CRISPR systems in nature. Cas10 forms a complex with crRNA and several Cas proteins that surveils prokaryotic cells for foreign RNA molecules and when they are detected it activates a cascade of interference activities. The synthesis of the cyclic oligoadenylate signalling molecule by Cas10 is a key aspect of the interference cascade. Despite structures of the Cas10 complex bound to target RNAs, the molecular mechanism by which Cas10 senses the bound state to licence interference is lacking. We identified five residues in Cas10, two in the Cas10 Palm2 domain and three in domain 4, that line the target RNA binding channel. We assessed the contribution of these residues to interference in the context of a cognate or mismatched target RNA. We found that the residues regulate whether a mismatched crRNA-target RNA duplex is able to activate interference . We purified two site-directed mutants of Cas10-Csm and show with cOA synthesis assays that they demonstrate enhanced discrimination of cognate versus mismatched target RNAs.
5' RNA capping is one of the major post-transcriptional modifications for the mobility and stability of RNA molecules. Measuring 5' caps of RNAs can help quantify expression levels of mRNAs and lncRNAs. One of the most s...5' RNA capping is one of the major post-transcriptional modifications for the mobility and stability of RNA molecules. Measuring 5' caps of RNAs can help quantify expression levels of mRNAs and lncRNAs. One of the most successful RNAseq methods that has used capping as a tool to quantify expression of transcription is Cap Analysis of Gene Expression (CAGE). Computational prediction of capping can therefore be used as a precursor to the prediction of transcriptional expression. Unfortunately, there is hardly any computational technique that has focused purely on predicting 5' capping. We have developed a transformer-based method for computational prediction of capping from DNA sequences. Our Llama and ReLoRA-based pre-training model, and Llama and LoRA-based fine-tuning model predict capping associated regions. We have used Leave-one-chromosome-out-cross-validation for our model. The average accuracy, and F1-score after fine-tuning the human genome hg19 (mouse genome mm9) for sequence classification is 79.12% (78.09%) and 78.11% (76.17%), respectively. We noted attention peak-based motifs having an aggregate Wilcoxon rank-sum p-value of 1.075e-10 between the attention peak region and the entire context window for the predicted positive motifs; an aggregate p-value of 7.17e-18 for the predicted negative motifs; and an aggregate p-value of 6.70e-08 between the attention peaks of the predicted positive and the predicted negative motifs. Our Llama-based approach aims to create a sequence-based framework to identify capping associated regions corresponding to CAGE peaks. Our analysis reveals statistically significant motifs from the regions of peak attention scores, which demonstrates biological relevance for some through their resident sites matching with known TF motifs.
Tumorigenesis is commonly driven by genetic mutations and disruptions in cellular signalling pathways. Here we show that the oncogenic overexpression of the RNase L inhibitor ABCE1, a component of interferon signalling,...Tumorigenesis is commonly driven by genetic mutations and disruptions in cellular signalling pathways. Here we show that the oncogenic overexpression of the RNase L inhibitor ABCE1, a component of interferon signalling, leads to distinct and extensive deviations in cancer transcriptomes. RNase L is a cellular endonuclease that cleaves RNA molecules at specific UU and UA dinucleotide sites. Typically, it is activated by viral infections and interferon signalling leading to targeting and destruction of UU/UA-rich viral and cellular mRNA. RNase L has also homoeostatic and tumour suppressive roles. Relying on patient transcriptomic data, we show that ABCE1 is extensively overexpressed in colorectal cancer (CRC) and to a lesser extent in lung cancer. This upregulation was strongly associated with the co-upregulation of almost all UU/UA rich transcripts and downregulation of those that are UU/UA-poor. Many of upregulated mRNAs code for proteins involved in cell cycle regulation and mitosis. Accordingly, the knockdown of ABCE1 in the CRC cell line HT29 led to reduced proliferation. Surprisingly, the very high ABCE1 levels were associated with improved patient survival in CRC. This observation might be related to an anti-ABCE1-specific immune response due to the induction of tumour-reactive cytotoxic T lymphocytes by ABCE1 as previously reported. In lung cancer ABCE1 overexpression is milder and is associated with poor survival. We report a measurable, specific, and extensive modulation of cancer transcriptomes by the oncogenic overexpression of a component of interferon signalling with unexpected outcomes on patient survival.
The epitranscriptome comprises chemical modifications found on RNA molecules that play essential roles in co- and post-transcriptional gene regulation. Dysregulation of these modifications has been implicated in various...The epitranscriptome comprises chemical modifications found on RNA molecules that play essential roles in co- and post-transcriptional gene regulation. Dysregulation of these modifications has been implicated in various diseases, fuelling interest in evaluating them as emerging biomarkers and therapeutic targets. Nanopore direct RNA sequencing provides a powerful platform for profiling diverse RNA modifications at single-molecule resolution, but the complexity of the signals requires advanced computational approaches for interpretation. Artificial intelligence, particularly deep learning (DL), has become central to this effort. While classical DL architectures such as convolutional and recurrent neural networks have been widely applied, more recent approaches employ specialized learning frameworks and ensemble strategies to address challenges of data scarcity, noise, and biological variability while providing higher resolution output. In this review, we summarize these developments and highlight future multidisciplinary opportunities at the intersection of artificial intelligence and biology for characterizing the epitranscriptome obtained with direct RNA nanopore sequencing.
HNRNPA2B1 contains two RRM domains and has been investigated for its possible role as an mA reader protein. The targetome of HNRNPA2B1 was shown to overlap with the mA methylation motif, but further investigations of its...HNRNPA2B1 contains two RRM domains and has been investigated for its possible role as an mA reader protein. The targetome of HNRNPA2B1 was shown to overlap with the mA methylation motif, but further investigations of its binding affinity for mA-containing RNAs have been less clear on the relative selectivity of HNRNPA2B1 for methylated transcripts. Our computational and experimental studies depict that when an mA modification is positioned in between the two RRM domains, and in the context of the GGACU motif that can be written by methyltransferases, the binding affinity is nearly identical and slightly less favourable to the unmodified sequence. Our study suggests that HNRNPA2B1 is not a (selective) reader but has high affinity for mA in a sequence-dependent manner. This can be attributed to the strong interactions conferred by AGG and UAG motifs rather than adenine or mA in the GGACU motif which are predicted to interact weakly, intercalating between the two RRMs or positioned outwards. Overall, our findings highlight the higher complexity of HNRNPA2B1 and RRM recognition properties compared to well-studied YTH domains in the recognition of mA, as well as modified and unmodified sequences.
Non-coding RNAs (ncRNAs) modulate protein-protein interactions (PPIs) by shaping the structural context in which binding occurs, rather than acting as direct inhibitors or enhancers. Using an integrative framework combin...Non-coding RNAs (ncRNAs) modulate protein-protein interactions (PPIs) by shaping the structural context in which binding occurs, rather than acting as direct inhibitors or enhancers. Using an integrative framework combining catRAPID RNA-protein interaction prediction and AlphaFold3-based structural modelling, we analysed RNA-dependent modulation of interaction states across physiological and oncogenic protein complexes. At the network level, physiological PPIs exhibit high shared ncRNA buffering capacity, whereas oncogenic interactions are characterized by reduced or absent RNA overlap. AlphaFold3 modelling of mutant IDH1/2 complexes illustrates how loss of RNA buffering permits excessive stabilization of enzyme-associated interfaces, reflected by directional changes in buried surface area (ΔBSA) and contact heterogeneity.
RNA-binding proteins (RBPs) constitute a diverse class of proteins essential for every stage of the gene expression process. Many RBPs are also linked to human diseases and pathologies. Understanding the molecular gramma...RNA-binding proteins (RBPs) constitute a diverse class of proteins essential for every stage of the gene expression process. Many RBPs are also linked to human diseases and pathologies. Understanding the molecular grammar of RNA-protein interactions is critical for deciphering the regulatory RNA code. This review provides a comprehensive overview of Massively Parallel Binding Assays (MPBAs), high-throughput techniques that use large libraries of RNA or protein variants to systematically investigate RNA-protein interactions. We describe the underlying principles of both and approaches, their applications, as well as their strengths and weaknesses. We conclude by outlining future directions and challenges in the field that will help drive the development of novel methods to better understand the RBP recognition code.
In response to stress, cells undergo gene expression reprogramming to cope with external stimuli. Cells utilize a conserved stress response mechanism called global downregulation of translation, leading to the storage of...In response to stress, cells undergo gene expression reprogramming to cope with external stimuli. Cells utilize a conserved stress response mechanism called global downregulation of translation, leading to the storage of translationally repressed mRNAs in RNA granules. During oxidative stress induced by H2O2, genes responsible for combating oxidative stress, such as catalases, are strongly induced. However, the post-transcriptional regulatory events affecting these genes during H2O2 stress are not well-explored. Scd6, an RGG-motif-containing protein in yeast, acts as a translational repressor through its interaction with eIF4G1. This study identifies the role of Scd6 in oxidative stress response by regulating cytoplasmic catalase T1 (CTT1). We observe that peroxide stress induces the assembly of Scd6 puncta, which do not colocalize with P-bodies or stress granules. Scd6 overexpression increased sensitivity, while deletion enhanced tolerance to H2O2 treatment. Increased ROS accumulation and decreased Ctt1 protein levels were observed upon Scd6 overexpression due to translation repression of CTT1 mRNA. CTT1 mRNA interacts with Scd6. smFISH analysis and RNA immunoprecipitation studies reveal that localization of Scd6 to puncta upon peroxide stress reduces its interaction with CTT1 mRNA, allowing derepression. The role of Scd6 in peroxide stress response is conserved since the human homolog LSm14A also localizes to puncta upon H2O2 stress, and its overexpression reduces survival in response to peroxide stress. Overall, this study identifies a unique example of translation regulation whereby stress-induced localization of the translation repressor protein to puncta leads to derepression of the target mRNA.
Tuberculosis, caused by , is an infectious disease linked to high mortality and can stay in the host cell longer when inactive. Multiple factors are linked to disease prognosis, including microRNAs. It is a diminutive si...Tuberculosis, caused by , is an infectious disease linked to high mortality and can stay in the host cell longer when inactive. Multiple factors are linked to disease prognosis, including microRNAs. It is a diminutive single-stranded RNA that regulates the expression of its target mRNAs. It consists of a brief nucleotide sequence, often 19-25 nucleotides in length, of non-coding RNA. It is also essential for early embryonic development, invasion, cell migration, apoptosis, and cell death. The review aims to analyse the transcriptome characteristics of various miRNAs in the tuberculosis prognosis. However, , circ-miRNA, and lncRNAs regulate gene expression. In TB patients' serum exosomes, expression was noticeably higher than in healthy individuals. Drug-resistant tuberculosis was related to , and , as well as , and in TB patients' lesion tissue and peripheral blood. Therefore, further miRNA research will focus on TB progression.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder whose pathophysiological mechanisms remain incompletely understood. Alternative splicing of transcription factors (TFs) may lead to significant functional...Polycystic ovary syndrome (PCOS) is a complex endocrine disorder whose pathophysiological mechanisms remain incompletely understood. Alternative splicing of transcription factors (TFs) may lead to significant functional consequences in the pathogenesis of PCOS. This study investigated genome-wide AS patterns and the expression of key TFs in PCOS to identify functionally relevant splicing events in a human dataset and validate them in a mouse model. Bioinformatics analysis of a PCOS RNA-seq dataset revealed 42 differentially spliced TFs, with enrichment in transcriptional regulation and metabolic pathways. Subsequent validation in a PCOS mouse model highlighted significant upregulation of and , along with a specific exon-skipping event in ;(Nfkb1-ES1496). Our findings demonstrate altered AS of critical TFs in PCOS, implicating dysregulated NF-κB signalling through splicing modulation as a potential contributor to the disorder, which may offer novel biomarker or therapeutic avenues.
Altered expression of box C/D small nucleolar RNAs (snoRNAs) is implicated in human diseases, including cancer. Box C/D snoRNAs canonically direct site-specific, 2'--methylation but the extent to which they participate i...Altered expression of box C/D small nucleolar RNAs (snoRNAs) is implicated in human diseases, including cancer. Box C/D snoRNAs canonically direct site-specific, 2'--methylation but the extent to which they participate in other functions remains unclear. To identify RNA interactions of box C/D snoRNAs in human cells, we applied two techniques based on UV crosslinking, proximity ligation and sequencing of RNA hybrids (CLASH and FLASH). These identified hundreds of novel snoRNA interactions with rRNA, snoRNAs and mRNAs. We developed an informatic pipeline to rigorously call interactions predicted to direct methylation. Multiple snoRNA-rRNA interactions identified were not predicted to direct RNA methylation. These potentially modulate methylation efficiency and/or contribute to folding dynamics during ribosomal subunit biogenesis. snoRNA-mRNA hybrids included 1,300 interactions between 117 snoRNA families and 940 mRNAs. Human U3 is substantially more abundant than other snoRNAs and represented about 50% of snoRNA-mRNA hybrids. The distribution of U3 interactions across mRNAs also differed from other snoRNAs. Following U3 depletion, mRNAs showing altered abundance were strongly enriched for U3 CLASH interactions. Most human snoRNAs are excised from pre-mRNA introns. Enrichment for snoRNA association with branch point regions of introns that contain snoRNA genes was common, suggesting widespread regulation of snoRNA maturation.