Affordable Access

deepdyve-link
Publisher Website

La involvement in tRNA and other RNA processing events including differences among yeast and other eukaryotes.

Authors
  • Blewett, Nathan H1
  • Maraia, Richard J2
  • 1 Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • 2 Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; Commissioned Corps, U.S. Public Health Service, Rockville, MD, USA. Electronic address: [email protected]
Type
Published Article
Journal
Biochimica et Biophysica Acta
Publisher
Elsevier
Publication Date
Apr 01, 2018
Volume
1861
Issue
4
Pages
361–372
Identifiers
DOI: 10.1016/j.bbagrm.2018.01.013
PMID: 29397330
Source
Medline
License
Unknown

Abstract

The conserved nuclear RNA-binding factor known as La protein arose in an ancient eukaryote, phylogenetically associated with another eukaryotic hallmark, synthesis of tRNA by RNA polymerase III (RNAP III). Because 3'-oligo(U) is the sequence-specific signal for transcription termination by RNAP III as well as the high affinity binding site for La, the latter is linked to the intranuclear posttranscriptional processing of eukaryotic precursor-tRNAs. The pre-tRNA processing pathway must accommodate a variety of substrates that are destined for both common steps as well as tRNA-specific events. The order of intranuclear pre-tRNA processing steps is mediated in part by three activities derived from interaction with La protein: 3'-end protection from untimely decay by 3' exonucleases, nuclear retention and chaperone activity that helps prevent pre-tRNA misfolding and mischanneling into offline pathways. A focus of this perspective will be on differences between yeast and mammals in the subcellular partitioning of pre-tRNA intermediates and differential interactions with La. We review how this is most relevant to pre-tRNA splicing which occurs in the cytoplasm of yeasts but in nuclei of higher eukaryotes. Also divergent is La architecture, comprised of three RNA-binding domains in organisms in all examined branches of the eukaryal tree except yeast, which have lost the C-terminal RNA recognition motif-2α (RRM2α) domain. We also review emerging data that suggest mammalian La interacts with nuclear pre-tRNA splicing intermediates and may impact this branch of the tRNA maturation pathway. Finally, because La is involved in intranuclear tRNA biogenesis we review relevant aspects of tRNA-associated neurodegenerative diseases. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.

Report this publication

Statistics

Seen <100 times