Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.

Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.
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核和细胞质聚腺苷酸结合蛋白 (PABP) 有利于不同的转录物和亚型。

DOI:
10.1093/nar/gkac263
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发表时间:
2022-05-06
影响因子:
14.9
通讯作者:
Pasquinelli, Amy E.
Pasquinelli, Amy E.
中科院分区:
生物学2区
文献类型:
--
作者:
Nicholson-Shaw, Angela L.;Kofman, Eric R.;Yeo, Gene W.;Pasquinelli, Amy E.

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大多数真核转录本3‘端附加的聚(A)-尾在其稳定性、核运输和翻译中起着关键作用。这些作用在很大程度上是由多聚(A)结合蛋白(PABP)介导的,PABP覆盖多聚(A)-尾巴,并与参与RNA生物发生和功能的各种蛋白质相互作用。虽然核PABP(PABPN)与新合成的PolyA-Tail结合,并被输出到细胞质的转录本上的细胞质PABP(PABPC)取代,但在这些PABPs上不同基因或同一基因的异构体的转录本的分布尚未在基因组范围内进行研究。在这里,我们分析了与内源性PABPN或PABPC免疫共沉淀的RNA在人类细胞中的身份、剪接状态、Poly(A)-尾巴大小和翻译状态。在稳定状态下,许多蛋白质编码和非编码的RNA显示出强烈的偏向,与PABPN或PABPC相关。虽然PABPN丰富的转录本更多地是不完全剪接的,并且含有更长的聚(A)尾巴,而PABPC丰富的RNA有更长的半衰期和更高的翻译效率,但也有奇怪的异常值。总体而言,我们的研究揭示了PABPN和PABPC结合的RNA的格局,提供了新的细节,支持并促进了对这些蛋白在Poly(A)-Tail合成、维持和功能中所起作用的当前理解。
The poly(A)-tail appended to the 3′-end of most eukaryotic transcripts plays a key role in their stability, nuclear transport, and translation. These roles are largely mediated by Poly(A) Binding Proteins (PABPs) that coat poly(A)-tails and interact with various proteins involved in the biogenesis and function of RNA. While it is well-established that the nuclear PABP (PABPN) binds newly synthesized poly(A)-tails and is replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A)-tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein-coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A)-tails and PABPC-enriched RNAs had longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A)-tail synthesis, maintenance, and function.
DOI: 10.1093/nar/gky955
发表时间: 2019-01-08
影响因子: 14.9
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期刊: EMBO JOURNAL
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