Distribution, organization an evolutionary history of La and LARPs in eukaryotes

Abstract

The fate of any cellular RNA is largely influenced by the nature and diversity of its interactions with various RNA-binding proteins (RBPs) leading to the formation of a biologically significant ribonucleoprotein (RNP) complex. La motif-containing proteins (composed of genuine La and La-related proteins (LARPs)) represent an evolutionary conserved family of RBPs that encompass a large range of crucial functions, involving coding and non-coding RNAs. In this work, we provide data that extend our previous knowledge on the distribution, organization and evolutionary history of this important protein family. Using a repertoire of 345 La motifcontaining proteins from 135 species representing all major eukaryotic lineages, we were able to pinpoint many lineage-specific variations in the structural organization of La and LARPs and propose new evolutive scenarios to explain their modern genomic distribution.

Parallel global profiling of plant TOR dynamics reveals a conserved role for LARP1 in translation

“…cell suspension culture proteomics [ Van Leene et al, 2019 ]), we defined a core set of bona fide TOR-sensitive phosphoproteins in Arabidopsis, including LARP1. LARP1 is an RNA-binding protein that is highly conserved in animals, plants, and most fungi ( Deragon, 2020 ). To elucidate how LARP1 acts downstream of TOR, we repeated our global profiling experiments in larp1 mutants.…”

“…The precise mechanisms of TOR-LARP1 signaling have been the subject of considerable recent controversy ( Berman et al, 2020 ), which we sought to partially address by providing an evolutionary perspective. The typical biomedical model for evolutionary comparison, S. cerevisiae , is unusual among eukaryotes because its genome does not include a complete LARP1 orthologue ( Deragon, 2020 ), which has limited progress on understanding the TOR-LARP1 pathway. Within mammalian model systems, investigations of LARP1 have focused primarily on the role of LARP1 in regulating cytosolic RP mRNA translation and/or stability, because virtually all vertebrate and many invertebrate cytosolic RP mRNAs begin with a 5′TOP motif ( Meyuhas et al, 1996 ; Parry et al, 2010 ).…”

Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1

“…Nevertheless, one could hypothesize that, in vivo, the PAM2w site, located within the largely unstructured and flexible N-terminus of LARP4B, could simultaneously contact two or more distinct MLLE units of neighbouring, poly(A)-bound PABC molecules. However, it should not go unnoticed that the cross-species sequence conservation is only high in the canonical part of the LARP4B–PAM2w motif, and comparably low in its variable part [ 59 ].…”

Parallel global profiling of plant TOR dynamics reveals a conserved role for LARP1 in protein translation

“…By comparing these results to distantly-related eukaryotes (e.g., yeast (Huber et al, 2009) and humans (Hsu et al, 2011;Yu et al, 2011)) and to orthogonal experimental approaches in Arabidopsis (e.g., cell suspension culture proteomics (Van Leene et al, 2019)), we defined a core set of bona fide TOR-sensitive phosphoproteins in Arabidopsis, including LARP1. LARP1 is an RNA-binding protein that is highly conserved in animals, plants, and most fungi (Deragon, 2020). To elucidate how LARP1 acts downstream of TOR, we repeated our global profiling experiments in larp1 mutants.…”

“…The precise mechanisms of TOR-LARP1 signaling have been the subject of considerable recent controversy (Berman et al, 2020), which we sought to partially address by providing an evolutionary perspective. The typical biomedical model for evolutionary comparison, S. cerevisiae, is unusual among eukaryotes because its genome does not include a complete LARP1 orthologue (Deragon, 2020), which has limited progress on understanding the TOR-LARP1 pathway. Within mammalian model systems, investigations of LARP1 have focused primarily on the role of LARP1 in regulating cytosolic RP mRNA translation and/or stability, because virtually all vertebrate cytosolic RP mRNAs begin with a 5′TOP motif.…”