Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions
Abstract Recent research has uncovered extensive variability in the boundaries of transcript isoforms, yet the functional consequences of this variation remain largely unexplored. Here, we systematically discriminate between the molecular phenotypes of overlapping coding and non‐coding transcription...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2014-02-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/msb.135068 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849234267357315072 |
|---|---|
| author | Ishaan Gupta Sandra Clauder‐Münster Bernd Klaus Aino I Järvelin Raeka S Aiyar Vladimir Benes Stefan Wilkening Wolfgang Huber Vicent Pelechano Lars M Steinmetz |
| author_facet | Ishaan Gupta Sandra Clauder‐Münster Bernd Klaus Aino I Järvelin Raeka S Aiyar Vladimir Benes Stefan Wilkening Wolfgang Huber Vicent Pelechano Lars M Steinmetz |
| author_sort | Ishaan Gupta |
| collection | DOAJ |
| description | Abstract Recent research has uncovered extensive variability in the boundaries of transcript isoforms, yet the functional consequences of this variation remain largely unexplored. Here, we systematically discriminate between the molecular phenotypes of overlapping coding and non‐coding transcriptional events from each genic locus using a novel genome‐wide, nucleotide‐resolution technique to quantify the half‐lives of 3′ transcript isoforms in yeast. Our results reveal widespread differences in stability among isoforms for hundreds of genes in a single condition, and that variation of even a single nucleotide in the 3′ untranslated region (UTR) can affect transcript stability. While previous instances of negative associations between 3′ UTR length and transcript stability have been reported, here, we find that shorter isoforms are not necessarily more stable. We demonstrate the role of RNA‐protein interactions in conditioning isoform‐specific stability, showing that PUF3 binds and destabilizes specific polyadenylation isoforms. Our findings indicate that although the functional elements of a gene are encoded in DNA sequence, the selective incorporation of these elements into RNA through transcript boundary variation allows a single gene to have diverse functional consequences. |
| format | Article |
| id | doaj-art-e00bdb37c6df4a8c847ef2bdd7902062 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2014-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-e00bdb37c6df4a8c847ef2bdd79020622025-08-20T04:03:12ZengSpringer NatureMolecular Systems Biology1744-42922014-02-0110211110.1002/msb.135068Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactionsIshaan Gupta0Sandra Clauder‐Münster1Bernd Klaus2Aino I Järvelin3Raeka S Aiyar4Vladimir Benes5Stefan Wilkening6Wolfgang Huber7Vicent Pelechano8Lars M Steinmetz9European Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Centre for Statistical Data AnalysisEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genomics Core FacilityEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitEuropean Molecular Biology Laboratory (EMBL), Genome Biology UnitAbstract Recent research has uncovered extensive variability in the boundaries of transcript isoforms, yet the functional consequences of this variation remain largely unexplored. Here, we systematically discriminate between the molecular phenotypes of overlapping coding and non‐coding transcriptional events from each genic locus using a novel genome‐wide, nucleotide‐resolution technique to quantify the half‐lives of 3′ transcript isoforms in yeast. Our results reveal widespread differences in stability among isoforms for hundreds of genes in a single condition, and that variation of even a single nucleotide in the 3′ untranslated region (UTR) can affect transcript stability. While previous instances of negative associations between 3′ UTR length and transcript stability have been reported, here, we find that shorter isoforms are not necessarily more stable. We demonstrate the role of RNA‐protein interactions in conditioning isoform‐specific stability, showing that PUF3 binds and destabilizes specific polyadenylation isoforms. Our findings indicate that although the functional elements of a gene are encoded in DNA sequence, the selective incorporation of these elements into RNA through transcript boundary variation allows a single gene to have diverse functional consequences.https://doi.org/10.1002/msb.135068alternative polyadenylationRNA stabilityRNA‐binding proteintranscript isoforms3′UTR |
| spellingShingle | Ishaan Gupta Sandra Clauder‐Münster Bernd Klaus Aino I Järvelin Raeka S Aiyar Vladimir Benes Stefan Wilkening Wolfgang Huber Vicent Pelechano Lars M Steinmetz Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions Molecular Systems Biology alternative polyadenylation RNA stability RNA‐binding protein transcript isoforms 3′UTR |
| title | Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions |
| title_full | Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions |
| title_fullStr | Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions |
| title_full_unstemmed | Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions |
| title_short | Alternative polyadenylation diversifies post‐transcriptional regulation by selective RNA–protein interactions |
| title_sort | alternative polyadenylation diversifies post transcriptional regulation by selective rna protein interactions |
| topic | alternative polyadenylation RNA stability RNA‐binding protein transcript isoforms 3′UTR |
| url | https://doi.org/10.1002/msb.135068 |
| work_keys_str_mv | AT ishaangupta alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT sandraclaudermunster alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT berndklaus alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT ainoijarvelin alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT raekasaiyar alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT vladimirbenes alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT stefanwilkening alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT wolfganghuber alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT vicentpelechano alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions AT larsmsteinmetz alternativepolyadenylationdiversifiesposttranscriptionalregulationbyselectivernaproteininteractions |