Eukaryotic Lsm proteins: lessons from bacteria. Nat Struct Mol Biol

Department of Microbiology, Immunology & Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 01/2006; 12(12):1031-6. DOI: 10.1038/nsmb1037
Source: PubMed


Over the last five years Sm-like (Lsm) proteins have emerged as important players in many aspects of RNA metabolism, including splicing, nuclear RNA processing and messenger RNA decay. However, their precise function in these pathways remains somewhat obscure. In contrast, the role of the bacterial Lsm protein Hfq, which bears striking similarities in both structure and function to Lsm proteins, is much better characterized. In this perspective, we have highlighted several functions that Hfq shares with Lsm proteins and put forward hypotheses based on parallels between the two that might further the understanding of Lsm function.

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Available from: Carol J Wilusz, Oct 05, 2015
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    • "These complexes regulate the stability and translation of mRNAs by facilitating base pairing interactions between small RNAs (sRNAs) and mRNAs [5-7]. In eukaryotes, more than 20 Sm protein homologs assemble into several distinct heteroheptameric rings [8]. There are two major eukaryotic Sm classes: the canonical Sm proteins and the Sm-like (Lsm) proteins [9]. "
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    ABSTRACT: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.
    Genome biology 01/2014; 15(1):R7. DOI:10.1186/gb-2014-15-1-r7 · 10.81 Impact Factor
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    • "Intriguingly, LSm proteins are homologous to the bacterial Hfq protein, which has similar functions in mRNA decay and bacteriophage Qβ replication. Hfq also acts as a chaperone to mediate regulation of gene expression by small RNAs (35), raising the possibility that LSm proteins may have similar roles in small RNA activity in eukaryotes. "
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    ABSTRACT: The P body protein LSm1 stimulates translation and replication of hepatitis C virus (HCV). As the liver-specific microRNA-122 (miR-122) is required for HCV replication and is associated with P bodies, we investigated whether regulation of HCV by LSm1 involves miR-122. Here, we demonstrate that LSm1 contributes to activation of HCV internal ribosome entry site (IRES)-driven translation by miR-122. This role for LSm1 is specialized for miR-122 translation activation, as LSm1 depletion does not affect the repressive function of miR-122 at 3' untranslated region (UTR) sites, or miR-122-mediated cleavage at a perfectly complementary site. We find that LSm1 does not influence recruitment of the microRNA (miRNA)-induced silencing complex to the HCV 5'UTR, implying that it regulates miR-122 function subsequent to target binding. In contrast to the interplay between miR-122 and LSm1 in translation, we find that LSm1 is not required for miR-122 to stimulate HCV replication, suggesting that miR-122 regulation of HCV translation and replication have different requirements. For the first time, we have identified a protein factor that specifically contributes to activation of HCV IRES-driven translation by miR-122, but not to other activities of the miRNA. Our results enhance understanding of the mechanisms by which miR-122 and LSm1 regulate HCV.
    Nucleic Acids Research 10/2013; 42(2). DOI:10.1093/nar/gkt941 · 9.11 Impact Factor
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    • "Hfq is bacterial homolog of eukaryotic Sm/Lsm family RNA-binding proteins (2). Eukaryotic Sm/Lsm proteins are involved in mRNA splicing (9–11). In Escherichia coli (Ec), Hfq is a homo-hexameric protein constituted by six subunits, with 102 amino acids in each subunit. "
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    ABSTRACT: The rpoS mRNA, which encodes the master regulator σ(S) of general stress response, requires Hfq-facilitated base pairing with DsrA small RNA for efficient translation at low temperatures. It has recently been proposed that one mechanism underlying Hfq action is to bridge a transient ternary complex by simultaneously binding to rpoS and DsrA. However, no structural evidence of Hfq simultaneously bound to different RNAs has been reported. We detected simultaneous binding of Hfq to rpoS and DsrA fragments. Crystal structures of AU6A•Hfq•A7 and Hfq•A7 complexes were resolved using 1.8- and 1.9-Å resolution, respectively. Ternary complex has been further verified in solution by NMR. In vivo, activation of rpoS translation requires intact Hfq, which is capable of bridging rpoS and DsrA simultaneously into ternary complex. This ternary complex possibly corresponds to a meta-stable transition state in Hfq-facilitated small RNA-mRNA annealing process.
    Nucleic Acids Research 04/2013; 41(11). DOI:10.1093/nar/gkt276 · 9.11 Impact Factor
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