The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei

The Canonical Poly (A) Polymerase PAP1 Polyadenylates Non-Coding RNAs and Is Essential for snoRNA Biogenesis in Trypanosoma brucei
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DOI:
10.1016/j.jmb.2017.04.015
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发表时间:
2017-10-27
影响因子:
5.6
通讯作者:
Michaeli, Shulamit
Michaeli, Shulamit
中科院分区:
生物学2区
文献类型:
--
作者:
Chikne, Vaibhav;Gupta, Sachin Kumar;Michaeli, Shulamit

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寄生虫布氏锥虫是非洲昏睡病的病原体,并且以其独特的RNA加工机制而闻名,该机制是包括利什曼原虫和克氏锥虫在内的所有动体纲动物所共有的。锥虫具有两种典型的RNA多聚(A)聚合酶(PAP),称为PAP 1和PAP 2。PAP1由该生物体中仅有的两个含有顺式剪接内含子的基因之一编码,其功能目前尚不清楚。在锥虫中,所有mRNA和非编码RNA如小核仁RNA(snoRNA)和长非编码RNA(IncRNA)经历反式剪接和聚腺苷酸化。在这里,我们表明,位于细胞核中的PAP 1的功能是多聚腺苷酸化非编码RNA,进行反式剪接和多聚腺苷酸化。PAP 1的主要底物是snoRNA和IncRNA。在PAP 1或PAP 2沉默的情况下,snoRNA的水平降低。snoRNA中间体的双重多聚腺苷酸化由PAP 2和PAP 1进行,并且需要mRNA的多聚腺苷酸化所必需的因子。PAP对前体snoRNA的双重聚腺苷酸化可能具有招募snoRNA加工所必需的机制的功能。(C)2017爱思唯尔有限公司版权所有
The parasite Trypanosome brucei is the causative agent of African sleeping sickness and is known for its unique RNA processing mechanisms that are common to all the kinetoplastidea including Leishmania and Trypanosome cruzi. Trypanosomes possess two canonical RNA poly (A) polymerases (PAPs) termed PAP1 and PAP2. PAP1 is encoded by one of the only two genes harboring cis-spliced introns in this organism, and its function is currently unknown. In trypanosomes, all mRNAs, and non-coding RNAs such as small nucleolar RNAs (snoRNAs) and long non-coding RNAs (IncRNAs), undergo trans-splicing and polyadenylation. Here, we show that the function of PAP1, which is located in the nucleus, is to polyadenylate non-coding RNAs, which undergo trans-splicing and polyadenylation. Major substrates of PAP1 are the snoRNAs and IncRNAs. Under the silencing of either PAP1 or PAP2, the level of snoRNAs is reduced. The dual polyadenylation of snoRNA intermediates is carried out by both PAP2 and PAP1 and requires the factors essential for the polyadenylation of mRNAs. The dual polyadenylation of the precursor snoRNAs by PAPs may function to recruit the machinery essential for snoRNA processing. (C) 2017 Elsevier Ltd. All rights reserved.