Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins
Structure of S. pombe telomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins
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DOI：
10.1080/15476286.2020.1836891
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发表时间：
2020-11-01
期刊：
影响因子：
4.1
通讯作者：
Feigon, Juli
中科院分区：
文献类型：
--
作者：
Basu, Ritwika;Eichhorn, Catherine D.;Feigon, Juli
la相关蛋白7 （LARP7）是一类结合RNA 3 '端并与其特异性靶RNA组成相关的RNA伴侣。在后生动物中，Larp7结合到长链非编码7SK RNA上，作为7SK RNP的核心成分，7SK RNP是真核生物转录的主要调节因子。在纤毛虫四膜虫中，LARP7蛋白p65是端粒酶的一个组成部分，端粒酶是维持真核生物染色体末端端粒DNA的必要核糖核蛋白复合物。p65对于端粒酶RNA （TER）与端粒酶逆转录酶的有序组装具有重要意义。出乎意料的是，裂糖酵母pombe Pof8最近被鉴定为LARP7蛋白和裂变酵母端粒酶的核心成分，对生物发生至关重要。LARP7蛋白具有保守的n端La基序和RRM1 （La模块）和c端RRM2，具有RRM2特异性的RNA底物识别，在p65中首次被结构表征为非典型RRM，命名为xRRM。本文介绍了S. pombe Pof8 RRM2的x射线晶体结构和核磁共振研究。Pof8 RRM2与p65和人类Larp7 xRRMs的序列和结构比较揭示了RNA结合的保守特征，其主要变异在于非规范螺旋α 3的长度。本研究表明，Pof8具有保守的xRRM特征，为TER识别和xRRM的定义特征提供了见解。
La-related proteins 7 (LARP7) are a class of RNA chaperones that bind the 3 ' ends of RNA and are constitutively associated with their specific target RNAs. In metazoa, Larp7 binds to the long non-coding 7SK RNA as a core component of the 7SK RNP, a major regulator of eukaryotic transcription. In the ciliate Tetrahymena the LARP7 protein p65 is a component of telomerase, an essential ribonucleoprotein complex that maintains the telomeric DNA at eukaryotic chromosome ends. p65 is important for the ordered assembly of telomerase RNA (TER) with telomerase reverse transcriptase. Unexpectedly, Schizosaccharomyces pombe Pof8 was recently identified as a LARP7 protein and a core component of fission yeast telomerase essential for biogenesis. LARP7 proteins have a conserved N-terminal La motif and RRM1 (La module) and C-terminal RRM2 with specific RNA substrate recognition attributed to RRM2, first structurally characterized in p65 as an atypical RRM named xRRM. Here we present the X-ray crystal structure and NMR studies of S. pombe Pof8 RRM2. Sequence and structure comparison of Pof8 RRM2 to p65 and human Larp7 xRRMs reveals conserved features for RNA binding with the main variability in the length of the non-canonical helix alpha 3. This study shows that Pof8 has conserved xRRM features, providing insight into TER recognition and the defining characteristics of the xRRM.