The RNA export factor TbMex67 connects transcription and RNA export in Trypanosoma brucei and sets boundaries for RNA polymerase I.

Protozoan Proteins / genetics RNA / metabolism RNA Polymerase I / genetics RNA Polymerase II / genetics RNA, Messenger / genetics Transcription Factors / metabolism Transcription, Genetic Trypanosoma brucei brucei / genetics

Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
09 06 2023
Historique:
accepted: 24 03 2023
revised: 21 03 2023
received: 08 11 2022
medline: 12 6 2023
pubmed: 19 4 2023
entrez: 18 4 2023
Statut: ppublish

Résumé

TbMex67 is the major mRNA export factor known to date in trypanosomes, forming part of the docking platform within the nuclear pore. To explore its role in co-transcriptional mRNA export, recently reported in Trypanosoma brucei, pulse labelling of nascent RNAs with 5-ethynyl uridine (5-EU) was performed with cells depleted of TbMex67 and complemented with a dominant-negative mutant (TbMex67-DN). RNA polymerase (Pol) II transcription was unaffected, but the procyclin loci, which encode mRNAs transcribed by Pol I from internal sites on chromosomes 6 and 10, showed increased levels of 5-EU incorporation. This was due to Pol I readthrough transcription, which proceeded beyond the procyclin and procyclin-associated genes up to the Pol II transcription start site on the opposite strand. Complementation by TbMex67-DN also increased Pol I-dependent formation of R-loops and γ-histone 2A foci. The DN mutant exhibited reduced nuclear localisation and binding to chromatin compared to wild-type TbMex67. Together with its interaction with chromatin remodelling factor TbRRM1 and Pol II, and transcription-dependent association of Pol II with nucleoporins, our findings support a role for TbMex67 in connecting transcription and export in T. brucei. In addition, TbMex67 stalls readthrough by Pol I in specific contexts, thereby limiting R-loop formation and replication stress.

Identifiants

DOI: 10.1093/nar/gkad251 PMID: 37070196 PMC: PMC10250216
pubmed: 37070196
pii: 7127222
doi: 10.1093/nar/gkad251
pmc: PMC10250216
doi:

Substances chimiques

Protozoan Proteins 0
RNA 63231-63-0
RNA Polymerase I EC 2.7.7.6
RNA Polymerase II EC 2.7.7.-
RNA, Messenger 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5177-5192

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Berta Pozzi (B)

Institute of Cell Biology, University of Bern, Bern, Switzerland.

Arunasalam Naguleswaran (A)

Institute of Cell Biology, University of Bern, Bern, Switzerland.

Francesca Florini (F)

Institute of Cell Biology, University of Bern, Bern, Switzerland.

Zahra Rezaei (Z)

Professor Alborzi Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Isabel Roditi (I)

Institute of Cell Biology, University of Bern, Bern, Switzerland.
ORCID: 0000-0003-2812-6513

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de protozoaire › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › DNA-directed RNA polymerases › RNA polymerase I › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › DNA-directed RNA polymerases › RNA polymerase II › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › The RNA export factor TbMex67 connects...
questionsmedicales.fr › Eucaryotes › Euglénozoaires › Kinetoplastida › Trypanosomatina › Trypanosoma › Trypanosoma brucei brucei › The RNA export factor TbMex67 connects...