ArticleNature structural & molecular biology2022
Alternative polyadenylation by sequential activation of distal and proximal PolyA sites.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- LENG8 granule regulates alternative polyadenylation in mammals.Nature communications · 2026Article
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Transcript diversity reflects deleterious RNA processing errors shaped by population size in metazoans.PLoS biology · 2026Article
- Elucidating the coordination of RNA processing using short-read and long-read RNA-sequencing methods.Nature reviews. Molecular cell biology · 2026Review
- 3'UTR shortening alleviates miRNA repression of mRNAs critical for muscle stem cell differentiation.The EMBO journal · 2026Article
- G-quadruplexes in the proximity 3'-UTR enhances alternative polyadenylation of Neogenin 1.iScience · 2025Article
- The Role of mRNA Alternative Processing in Mammalian Neurodevelopment.International journal of molecular sciences · 2025Review
- Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3' ends.Cell reports · 2025Article
- Altered polyadenylation site usage in SERPINA1 3'UTR in response to cellular stress affects A1AT protein expression.Scientific reports · 2025Article
- APALORD: An R-based tool for differential alternative polyadenylation analysis of long-read RNA-seq data.bioRxiv : the preprint server for biology · 2025Article
- The regulation and function of post-transcriptional RNA splicing.Nature reviews. Genetics · 2025Review
- Review
- Coupling of alternative splicing and alternative polyadenylation.Acta biochimica et biophysica Sinica · 2024Review
- Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus.Computational and structural biotechnology journal · 2024Article
- The MTR4/hnRNPK complex surveils aberrant polyadenylated RNAs with multiple exons.Nature communications · 2024Article
- Nuclear mRNA decay: regulatory networks that control gene expression.Nature reviews. Genetics · 2024Review
- Light regulates widespread plant alternative polyadenylation through the chloroplast.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dynamic Alternative Polyadenylation duringGenes · 2024Article
- Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analogous to alternative splicing, alternative polyadenylation (APA) has long been thought to occur independently at proximal and distal polyA sites. Using fractionation-seq, we unexpectedly identified several hundred APA genes in human cells whose distal polyA isoforms are retained in chromatin/nuclear matrix and whose proximal polyA isoforms are released into the cytoplasm. Global metabolic PAS-seq and Nanopore long-read RNA-sequencing provide further evidence that the strong distal polyA sites are processed first and the resulting transcripts are subsequently anchored in chromatin/nuclear matrix to serve as precursors for further processing at proximal polyA sites. Inserting an autocleavable ribozyme between the proximal and distal polyA sites, coupled with a Cleave-seq approach that we describe here, confirms that the distal polyA isoform is indeed the precursor to the proximal polyA isoform. Therefore, unlike alternative splicing, APA sites are recognized independently, and in many cases, in a sequential manner. This provides a versatile strategy to regulate gene expression in mammalian cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.