Alternative polyadenylation diversifies post-transcriptional regulation by selective RNA-protein interactions
Alternative polyadenylation diversifies post-transcriptional regulation by selective RNA-protein interactions
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DOI：
10.1002/msb.135068
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发表时间：
2014-02-01
影响因子：
9.9
通讯作者：
Steinmetz, Lars M.
中科院分区：
文献类型：
--
作者：
Gupta, Ishaan;Clauder-Muenster, Sandra;Steinmetz, Lars M.
一个基因可以通过多聚腺苷酸化产生多种亚型。这项研究表明，每个基因的异构体可以有不同的分子表型，如RNA的稳定性和与蛋白质的相互作用，多样化的基因组功能的潜力。不同的转录后命运的3 '转录异构体揭示了在全基因组水平。新的技术，准确地测量异构体特异性的稳定性和蛋白质结合，因此证明了两者的广泛变异。即使是几个核苷酸的变异也与转录物稳定性的变异有关。转录物与PUF 3的结合和随后的不稳定发生在一种异构体中，具体方式。摘要最近的研究发现转录物同工型边界存在广泛的变异性，但这种变异的功能后果在很大程度上仍未得到探索。在这里，我们系统地区分重叠的编码和非编码转录事件的分子表型，从每个基因位点使用一种新的全基因组，核苷酸分辨率技术，以量化的3 '转录异构体在酵母中的半衰期。我们的研究结果揭示了在单一条件下数百个基因的异构体之间的稳定性存在广泛差异，并且3 '非翻译区（UTR）中甚至单个核苷酸的变化都可以影响转录物的稳定性。虽然先前已经报道了3 ' UTR长度和转录物稳定性之间的负相关性，但是在这里，我们发现较短的同种型不一定更稳定。我们证明了RNA-蛋白质相互作用在调节异构体特异性稳定性中的作用，表明PUF 3结合并使特异性聚腺苷酸化异构体不稳定。我们的研究结果表明，虽然基因的功能元件是在DNA序列中编码的，这些元件通过转录边界变异选择性地掺入RNA允许单个基因具有不同的功能后果。
SynopsisimageA single gene can give rise to many isoforms via alternative polyadenylation. This study demonstrates that isoforms of each gene can have different molecular phenotypes like RNA stability and interaction with proteins, diversifying the functional potential of the genome.Divergent post-transcriptional fates of 3 ' transcript isoforms are revealed at a genome-wide level.New techniques are presented that accurately measure isoform-specific stability and protein binding, thus demonstrating widespread variation in both.Even variations of a few nucleotides are associated with variations in transcript stability.Transcript binding to PUF3 and subsequent destabilization occurs in an isoform-specific manner.AbstractRecent 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.