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RNA mimicry in post‐transcriptional regulation by aminoacyl tRNA synthetases

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Abstract Aminoacyl tRNA synthetases (aaRS) are well studied for their roles in tRNA charging with cognate amino acid. Nevertheless, numerous lines of evidence indicate that these proteins have roles other than tRNA charging. These include coordination of cellular signaling cascades, induction of cytokines outside the cell and transcription regulation. Herein, we focus on their roles in post‐transcriptional regulation of mRNA expression. We describe functions that are related to antitermination of transcription, RNA splicing and mRNA translation. Cases were recognition of mRNA by the aaRS involves recognition of tRNA‐like structures are described. Such recognition may be achieved by repurposing tRNA‐binding domains or through domains added to the aaRS later in evolution. Furthermore, we describe cases in which binding by aaRS is implicated in autogenous regulation of expression. Overall, we propose RNA‐mimicry as a common mode of interaction between aaRS and mRNA which allows efficient expression regulation. This article is categorized under: RNA Processing > tRNA Processing RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications Translation > Translation Regulation
Different interaction magnitude between aaRS and cognate tRNA. HisRS (left) interacts with its tRNA only through its anticodon and catalytic binding domains. ValRS (right) on the other hand, interacts with various additional regions, including the D and T loops. Both structures are of T. thermophilus proteins, and were modeled by PyMOL
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Different modes of translation regulation through an anticodon mimic. aaRSs bind an element that resembles the anticodon region of their cognate tRNA (structures of these elements were predicted according to (Mori, Hamada, & Asai, ) and depicted at the left in each transcript). aaRS binding may exert various impacts on translation. (a) Anticodon‐like structures with a CGU triplet are present at the 5′ leader (Domains 2 and 4) of thrS mRNA and mediate binding of a homodimeric ThrRS complex. Binding interferes with the interaction between the small ribosomal subunit and the Shine‐Dalgarno sequence, thus inhibiting translation of ThrRS protein. (b) Binding of GlyRS to an anticodon‐mimic with an ACC sequence positioned in the IRES region of HIV transcript enhances the association of the 40S small ribosomal subunit. In this case, binding impose an activating role on translation. Intriguingly, while ACC is a possible anticodon for glycine, there are no natural tRNAs that carry this triplet in human cells (Chan & Lowe, ). (c) ValRS binds a tRNA‐like structure at the 3′ end of TYMV transcript and adds a valine at the end of the transcript. This leads to association of the elongation factor EF1A and enhances translation through the 5′ end of the mRNA. (d) HisRS binds an anticodon like element within its open reading frame (ORF) and represses translation
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Cellular roles of aaRSs. Schematic diagram of functions of aaRSs, described in this Review. Light green section indicates functions that involve RNA binding, while the light red section indicates functions that are non‐RNA mediated. aaRSs involved in each non‐tRNA function are indicated. The prefix indicates the organism from which the majority of work was obtained: hs H. sapiens, sc S. cerevisiae, ec E. coli, bs Bacillus subtilis, nc N. crassa, tymv Turnip yellow mosaic virus
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Translation > Translation Regulation
RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition
RNA Processing > tRNA Processing

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