Architecture of the U6 snRNP reveals specific recognition of 3'-end processed U6 snRNA.

Architecture of the U6 snRNP reveals specific recognition of 3'-end processed U6 snRNA.
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DOI:
10.1038/s41467-018-04145-4
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发表时间:
2018-05-01
影响因子:
16.6
通讯作者:
Butcher SE
Butcher SE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Montemayor EJ;Didychuk AL;Yake AD;Sidhu GK;Brow DA;Butcher SE

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剪接体从前体信使RNA(pre-mRNA)去除内含子以产生成熟mRNA。在催化之前,剪接体从头组装到前mRNA底物上。在这个组装过程中,U6小核RNA(snRNA)经历了广泛的结构重塑。该重塑过程的早期阶段由U6 snRNP蛋白Prp 24和Lsm 2 -8杂七聚体环陪伴。我们现在报告的结构的U6 snRNP从酿酒酵母。该结构揭示了蛋白质-蛋白质接触,将Lsm 2 -8定位在Prp 24的伴侣“活性位点”附近。该结构还显示了Lsm 2 -8环如何特异性识别在其3′端经过转录后修饰的U6 snRNA,从而阐明了U6 snRNP选择性地将3′端加工的U6 snRNA募集到剪接体中的机制。此外,结构揭示了Lsm 8的C-末端区域和参与mRNA衰变的细胞质Lsm 1蛋白之间的意外同源性。剪接体从前体信使RNA中去除内含子以产生成熟的mRNA。在这里,作者报告了U6 snRNP晶体结构,该结构提供了关于U6 snRNA的3′磷酸如何被Lsm 2 -8复合物识别以及U6 snRNP蛋白如何隔离和保护活性位点RNA直到其组装成剪接体的见解。
The spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) undergoes extensive structural remodeling. The early stages of this remodeling process are chaperoned by U6 snRNP proteins Prp24 and the Lsm2–8 heteroheptameric ring. We now report a structure of the U6 snRNP from Saccharomyces cerevisiae. The structure reveals protein–protein contacts that position Lsm2–8 in close proximity to the chaperone “active site” of Prp24. The structure also shows how the Lsm2–8 ring specifically recognizes U6 snRNA that has been post-transcriptionally modified at its 3′ end, thereby elucidating the mechanism by which U6 snRNPs selectively recruit 3′ end-processed U6 snRNA into spliceosomes. Additionally, the structure reveals unanticipated homology between the C-terminal regions of Lsm8 and the cytoplasmic Lsm1 protein involved in mRNA decay. The spliceosome removes introns from precursor messenger RNAs to produce mature mRNAs. Here the authors report a U6 snRNP crystal structure that provides insight on how the 3′ phosphate of U6 snRNA is recognized by the Lsm2–8 complex and how the U6 snRNP proteins sequester and protect the active site RNA until it is assembled into the spliceosome.
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