Pozzi, Berta; Naguleswaran, Arunasalam; Florini, Francesca; Rezaei, Zahra; Roditi, Isabel (2023). The RNA export factor TbMex67 connects transcription and RNA export in Trypanosoma brucei and sets boundaries for RNA polymerase I. Nucleic acids research, 51(10), pp. 5177-5192. Oxford University Press 10.1093/nar/gkad251
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology |
UniBE Contributor: |
Pozzi, Maria Berta, Naguleswaran, Arunasalam, Florini, Francesca, Roditi, Isabel |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
1362-4962 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
19 Apr 2023 09:46 |
Last Modified: |
10 Jun 2023 00:14 |
Publisher DOI: |
10.1093/nar/gkad251 |
PubMed ID: |
37070196 |
BORIS DOI: |
10.48350/181838 |
URI: |
https://boris.unibe.ch/id/eprint/181838 |
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