Competing RNA pairings in complex alternative splicing of a 3' variable region.

Competing RNA pairings in complex alternative splicing of a 3' variable region.
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DOI:
10.1261/rna.066225.118
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发表时间:
2018-11
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Jin Y
Jin Y
中科院分区:
其他
文献类型:
--
作者:
Pan H;Shi Y;Chen S;Yang Y;Yue Y;Zhan L;Dai L;Dong H;Hong W;Shi F;Jin Y

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选择性前体mRNA剪接显著地扩展了真核生物中的蛋白质多样性。果蝇PGRP-LC可以产生三种主要的3′剪接异构体,这些异构体表现出不同的先天免疫识别和对各种微生物感染的防御。然而,3′可变区独特的偏性剪接模式背后的调控机制仍不清楚。在这里,我们表明,竞争RNA配对控制的3′可变区的独特剪接的果蝇PGRP-LC前mRNA。我们揭示了这些RNA配对通过激活近端3′剪接位点并同时掩蔽内含子近端5′剪接位点,结合RNA配对的物理竞争来共同调节3′变体选择的三种作用。我们还发现,竞争RNA配对调节果蝇CG 42235和Pip高度复杂的3′可变区的选择性剪接。我们的研究结果将有助于更好地理解高度复杂的选择性剪接以及高度可变的3′加工的调控机制。
Alternative pre-mRNA splicing remarkably expands protein diversity in eukaryotes. Drosophila PGRP-LC can generate three major 3′ splice isoforms that exhibit distinct innate immune recognition and defenses against various microbial infections. However, the regulatory mechanisms underlying the uniquely biased splicing pattern at the 3′ variable region remain unclear. Here we show that competing RNA pairings control the unique splicing of the 3′ variable region of Drosophila PGRP-LC pre-mRNA. We reveal three roles by which these RNA pairings jointly regulate the 3′ variant selection through activating the proximal 3′ splice site and concurrently masking the intron-proximal 5′ splice site, in combination with physical competition of RNA pairing. We also reveal that competing RNA pairings regulate alternative splicing of the highly complex 3′ variable regions of Drosophila CG42235 and Pip. Our findings will facilitate a better understanding of the regulatory mechanisms of highly complex alternative splicing as well as highly variable 3′ processing.
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