Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate.
Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate.
复制标题
DOI：
10.1016/j.celrep.2017.02.046
复制
发表时间：
2017-03-14
期刊：
影响因子：
8.8
通讯作者：
Bertrand E
中科院分区：
文献类型：
--
作者：
Giacometti S;Benbahouche NEH;Domanski M;Robert MC;Meola N;Lubas M;Bukenborg J;Andersen JS;Schulze WM;Verheggen C;Kudla G;Jensen TH;Bertrand E
核帽结合复合体(CBC)刺激被帽RNA的加工反应，包括它们的剪接、3‘端的形成、降解和运输。CBC效应对于单个RNA家族是特殊的，但这种选择性是如何实现的仍然是难以捉摸的。在这里，我们分析了三个已知的影响不同RNA物种的主要CBC伙伴。ARS2刺激几种转录类型的3‘端形成/转录终止，ZC3H18刺激一系列不同RNA的降解，并且phax在前小核RNA/小核仁RNA(Pre-SnRNA/snoRNA)运输中发挥作用。令人惊讶的是，这些蛋白质都与带帽的RNA结合，而对给定的转录本没有强烈的偏好，而且它们的稳态结合与它们的功能相关性很差。尽管如此，phax和ZC3H18仍在争夺CBC结合，我们证明了这种竞争结合在功能上是相关的。我们进一步表明，含CBC的复合体在体内是短暂的，因此我们认为RNA的命运涉及相互排斥的CBC复合体的瞬时形成，这可能只有在RNA生物发生的特定检查点才是重要的。Phax和ZC3H18竞争与核CBC的结合phax和ZC3H18对SnRNA前体的命运有相反的影响，而其他RNA phax、ARS2和ZC3H18结合的封顶RNA对给定的转录本没有强烈的偏好，含CBC的复合体在体内生存时间很短，寿命只有几秒钟。核CBC在RNA生物发生中发挥着不同的作用，目前尚不清楚单个RNA家族是如何实现选择性作用的。贾科梅蒂等人。这表明，RNA的命运涉及形成短暂的、相互排斥的CBC复合体，这可能只在RNA生物发生的特定检查点产生影响。
The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3′-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3′-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis. PHAX and ZC3H18 compete for binding to the nuclear CBC PHAX and ZC3H18 have opposite effects on the fate of snRNA precursors and other RNAs PHAX, ARS2, and ZC3H18 bind capped RNAs without strong preference for given transcripts CBC-containing complexes are short lived in vivo, with a lifetime of a few seconds The nuclear CBC plays diverse roles in RNA biogenesis and it is not clear how selective effects are achieved for individual RNA families. Giacometti et al. suggest that RNA fate involves the formation of short-lived, mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.