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The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives.

ABSTRACT: La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell-ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU-3'-OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor-tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that helps to prevent their misfolding. Related to this, we review evidence that suggests that La and its link to RNAP III were significant in the great expansions of the tRNAomes that occurred in eukaryotes. Four families of La-related proteins (LARPs) emerged during eukaryotic evolution with specialized functions. We provide an overview of the high-resolution structural biology of La and LARPs. LARP7 family members most closely resemble La but function with a single RNAP III nuclear transcript, 7SK, or telomerase RNA. A cytoplasmic isoform of La protein as well as LARPs 6, 4, and 1 function in mRNA metabolism and translation in distinct but similar ways, sometimes with the poly(A)-binding protein, and in some cases by direct binding to poly(A)-RNA. New structures of LARP domains, some complexed with RNA, provide novel insights into the functional versatility of these proteins. We also consider LARPs in relation to ancestral La protein and potential retention of links to specific RNA-related pathways. One such link may be tRNA surveillance and codon usage by LARP-associated mRNAs. WIREs RNA 2017, 8:e1430. doi: 10.1002/wrna.1430 For further resources related to this article, please visit the WIREs website.

SUBMITTER: Maraia RJ

PROVIDER: S-EPMC5647580 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives.

Maraia Richard J RJ Mattijssen Sandy S Cruz-Gallardo Isabel I Conte Maria R MR

Wiley interdisciplinary reviews. RNA 20170807 6

La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell-ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU-3'-OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor-tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that h ...[more]

PMID: 28782243

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Project description:The TRIM-NHL family of proteins shares a conserved domain architecture and play crucial roles in stem cell biology, fertility, and development. This review synthesizes new insights that have revolutionized our understanding of the molecular and biological functions of TRIM-NHL proteins. Multiple TRIM-NHLs have been shown to bind specific RNA sequences and structures. X-ray crystal structures of TRIM-NHL proteins in complex with RNA ligands reveal versatile modes of RNA recognition by the NHL domain. Functional and genetic analyses show that TRIM-NHL RNA-binding proteins negatively regulate the protein expression from the target mRNAs that they bind. This repressive activity plays a crucial role in controlling stem cell fate in the developing brain and differentiating germline. To highlight these paradigms, we focus on several of the most-extensively studied TRIM-NHL proteins, specifically Drosophila and vertebrate TRIM71, among others. Brat is essential for development and regulates key target mRNAs to control differentiation of germline and neural stem cells. TRIM71 is also required for development and promotes stem cell proliferation while antagonizing differentiation. Moreover, TRIM71 can be utilized to help reprogram fibroblasts into induced pluripotent stem cells. Recently discovered mutations in TRIM71 cause the neurodevelopmental disease congenital hydrocephalus and emphasize the importance of its RNA-binding function in brain development. Further relevance of TRIM71 to disease pathogenesis comes from evidence linking it to several types of cancer, including liver and testicular cancer. Collectively, these advances demonstrate a primary role for TRIM-NHL proteins in the post-transcriptional regulation of gene expression in crucial biological processes. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability.

Dataset Information

The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives.

Publications

The La and related RNA-binding proteins (LARPs): structures, functions, and evolving perspectives.

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