Conserved and divergent features of the structure and function of La and La-related proteins (LARPs).
Conserved and divergent features of the structure and function of La and La-related proteins (LARPs).
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DOI：
10.1016/j.bbagrm.2010.01.011
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发表时间：
2010-05
影响因子：
4.7
通讯作者：
Maraia, Richard J.
中科院分区：
文献类型：
--
作者：
Bayfield, Mark A.;Yang, Ruiqing;Maraia, Richard J.
关键词：
真正的La蛋白包含两个RNA结合基序，一个La基序（LAM）和一个RNA识别基序（RRM），以独特的方式排列以结合RNA。这些蛋白与多种细胞rna相互作用，并在两大类别中表现出活性：i)通过结合其共同的含有uu -3 ' oh的末端，促进新生pol III转录物（包括前体trna）的代谢，ii)调节涉及未知结合机制的某些mrna的翻译。几种La-RNA晶体结构的表征以及生化研究揭示了它们独特的双基序结构域结构，以及LAM如何识别UUU-3'OH，而RRM如何结合前trna的其他部分。最近对保守La相关蛋白（LARPs）不同家族成员的研究表明，其中一些具有与真正的La蛋白相关的活性，这表明它们的UUU-3'OH结合模式已被用于特定snRNP的组装和调控（例如hLARP7/PIP7S组装7SK snRNA）。对其他LARP家族成员（即hLARP4， hLARP6）的分析表明，RNA结合模式更多样化，细胞质mrna相关功能更特化。因此，虽然真正的La蛋白在snRNA和mRNA相关功能中都表现出广泛的参与，但不同的LARP家族可能在snRNA或mRNA相关功能中进化出专门的活性。在这篇综述中，我们总结了近年来对La蛋白的结构和功能及其在tRNA加工和RNP组装动力学中的作用的理解，以及不同larp的研究进展。
Genuine La proteins contain two RNA binding motifs, a La motif (LAM) followed by a RNA recognition motif (RRM), arranged in a unique way to bind RNA. These proteins interact with an extensive variety of cellular RNAs and exhibit activities in two broad categories: i) to promote the metabolism of nascent pol III transcripts, including precursor-tRNAs, by binding to their common, UUU-3’OH containing ends, and ii) to modulate the translation of certain mRNAs involving an unknown binding mechanism. Characterization of several La-RNA crystal structures as well as biochemical studies reveal insight into their unique two-motif domain architecture and how the LAM recognizes UUU-3’OH while the RRM binds other parts of a pre-tRNA. Recent studies of members of distinct families of conserved La-related proteins (LARPs) indicate that some of these harbor activity related to genuine La proteins, suggesting that their UUU-3’OH binding mode has been appropriated for the assembly and regulation of a specific snRNP (e.g., 7SK snRNA assembly by hLARP7/PIP7S). Analyses of other LARP family members (i.e., hLARP4, hLARP6) suggest more diverged RNA binding modes and specialization for cytoplasmic mRNA-related functions. Thus it appears that while genuine La proteins exhibit broad general involvement in both snRNA-related and mRNA-related functions, different LARP families may have evolved specialized activities in either snRNA or mRNA related functions. In this review, we summarize recent progress that has led to greater understanding of the structure and function of La proteins and their roles in tRNA processing and RNP assembly dynamics, as well as progress on the different LARPs.
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