The La Protein

Abstract

Ubiquitous in eukaryotic cells, the La protein associates with the 3' termini of many newly synthesized small RNAs. RNAs bound by the La protein include all nascent transcripts made by RNA polymerase III as well as certain small RNAs synthesized by other RNA polymerases. Recent genetic and biochemical analyses have revealed that binding by the La protein protects the 3' ends of these RNAs from exonucleases. This La-mediated stabilization is required for the normal pathway of pre-tRNA maturation, facilitates assembly of small RNAs into functional RNA-protein complexes, and contributes to nuclear retention of certain small RNAs. Studies of mutant La proteins have given some insights into how the La protein specifically recognizes its RNA targets. However, many questions remain regarding the molecular mechanisms by which La protein binding influences multiple steps in small RNA biogenesis. This review focuses on the roles of the La protein in small RNA biogenesis and also discusses data that implicate the La protein in the translation of specific mRNAs.

The C-terminal domain of coilin interacts with Sm proteins and U snRNPs

“…Additionally, U6 snRNA lacks a canonical Smbinding site, but contains a stretch of 3′ uridine residues that, following transcription termination, are initially bound by the La protein (reviewed in Wolin and Cedervall 2002). Subsequently, La is replaced by a heptameric ring composed of the Lsm (Sm-like) proteins 2-8.…”

BCR/ABL, mRNA translation and apoptosis

“…72 Although La antigen is primarily localized in the nucleus, it is also present in the cytoplasm, and increases there under certain conditions. 143,144 For example, in poliovirus-infected cells, La is redirected to the cytoplasm, where it is believed to interact with the 5 0 UTR of poliovirus mRNA to positively influence its translation. 144,145 In addition to multiple virus-derived mRNAs, La has also been reported to interact with cellular mRNAs.…”

“…143,144 For example, in poliovirus-infected cells, La is redirected to the cytoplasm, where it is believed to interact with the 5 0 UTR of poliovirus mRNA to positively influence its translation. 144,145 In addition to multiple virus-derived mRNAs, La has also been reported to interact with cellular mRNAs. Recently, the La antigen was reported to activate IRES-dependent translation of the immunoglobulin heavy chain binding protein (BiP) mRNA upon interaction with its 5 0 UTR, 146 and of the X-linked inhibitor of apoptosis (XIAP) mRNA.…”

“…72 This suggests that the La protein has a general role in the regulation of mRNA translation rather than controlling IRES-dependent translation only. 144 Indeed, two recent reports indicate that La can regulate translation of a specific subset of mRNAs, the TOP mRNAs, containing a terminal oligopyrimidine tract sequence in their 5 0 UTR, in a casein kinase 2 (CK2)-dependent manner. [148][149][150] Note that CK2 plays an important role in the proliferation of BCR/ABL-expressing cells, 151 thus it is also possible that CK2-dependent regulation of La might lead to translation modulation of the expression of factors important for the growth advantage of CML cells.…”

Direct antigen presentation by DC shapes the functional CD8+ T‐cell repertoire against the nuclear self‐antigen La‐SSB

“…La is a ubiquitous nuclear protein involved in the termination of RNA polymerase III transcripts, and is found stably associated in the Ro/La ribonucleoprotein complex [18]. Autoantibodies to this protein are observed in 30 and 90% of patients with systemic lupus erythematosus and Sjögren's syndrome, respectively [19] indicating it is a clinically significant autoimmune target.…”