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Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export

Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcr...

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Autores principales: Chatterjee, Kunal, Majumder, Shubhra, Wan, Yao, Shah, Vijay, Wu, Jingyan, Huang, Hsiao-Yun, Hopper, Anita K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749166/
https://www.ncbi.nlm.nih.gov/pubmed/29212662
http://dx.doi.org/10.1101/gad.305904.117
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author Chatterjee, Kunal
Majumder, Shubhra
Wan, Yao
Shah, Vijay
Wu, Jingyan
Huang, Hsiao-Yun
Hopper, Anita K.
author_facet Chatterjee, Kunal
Majumder, Shubhra
Wan, Yao
Shah, Vijay
Wu, Jingyan
Huang, Hsiao-Yun
Hopper, Anita K.
author_sort Chatterjee, Kunal
collection PubMed
description Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67–Mtr2 (TAP–p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67–Mtr2 can substitute for Los1 in los1Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67–Mtr2 functions in primary nuclear export for a subset of yeast tRNAs.
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spelling pubmed-57491662018-05-01 Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export Chatterjee, Kunal Majumder, Shubhra Wan, Yao Shah, Vijay Wu, Jingyan Huang, Hsiao-Yun Hopper, Anita K. Genes Dev Research Paper Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67–Mtr2 (TAP–p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67–Mtr2 can substitute for Los1 in los1Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67–Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. Cold Spring Harbor Laboratory Press 2017-11-01 /pmc/articles/PMC5749166/ /pubmed/29212662 http://dx.doi.org/10.1101/gad.305904.117 Text en © 2017 Chatterjee et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Chatterjee, Kunal
Majumder, Shubhra
Wan, Yao
Shah, Vijay
Wu, Jingyan
Huang, Hsiao-Yun
Hopper, Anita K.
Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title_full Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title_fullStr Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title_full_unstemmed Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title_short Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export
title_sort sharing the load: mex67–mtr2 cofunctions with los1 in primary trna nuclear export
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749166/
https://www.ncbi.nlm.nih.gov/pubmed/29212662
http://dx.doi.org/10.1101/gad.305904.117
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