Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei

0554311 - BC 2022 RIV GB eng J - Článek v odborném periodiku
Mishra, A. - Kaur, J. - McSkimming, D. - Hegedüsová, Eva - Dubey, A.P. - Ciganda, M. - Paris, Zdeněk - Read, L. K.
Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei.
Molecular Microbiology. Roč. 116, č. 3 (2021), s. 827-840. ISSN 0950-382X. E-ISSN 1365-2958
Grant CEP: GA MŠMT(CZ) EF16_019/0000759; GA ČR(CZ) GA20-11585S
Institucionální podpora: RVO:60077344
Klíčová slova: sr proteins * binding * transport * complex * mex67-mtr2 * decay * fish * mRNA export * nucleoporin * RNA binding protein * RNAseq * trypanosome
Obor OECD: Parasitology
Impakt faktor: 3.979, rok: 2021
Způsob publikování: Open access
https://onlinelibrary.wiley.com/doi/10.1111/mmi.14773

Kinetoplastids, including Trypanosoma brucei, control gene expression primarily at the posttranscriptional level. Nuclear mRNA export is an important, but understudied, step in this process. The general heterodimeric export factors, Mex67/Mtr2, function in the export of mRNAs and tRNAs in T. brucei, but RNA binding proteins (RBPs) that regulate export processes by controlling the dynamics of Mex67/Mtr2 ribonucleoprotein formation or transport have not been identified. Here, we report that DRBD18, an essential and abundant T. brucei RBP, associates with Mex67/Mtr2 in vivo, likely through its direct interaction with Mtr2. DRBD18 downregulation results in partial accumulation of poly(A)(+) mRNA in the nucleus, but has no effect on the localization of intron-containing or mature tRNAs. Comprehensive analysis of transcriptomes from whole-cell and cytosol in DRBD18 knockdown parasites demonstrates that depletion of DRBD18 leads to impairment of nuclear export of a subset of mRNAs. CLIP experiments reveal the association of DRBD18 with several of these mRNAs. Moreover, DRBD18 knockdown leads to a partial accumulation of the Mex67/Mtr2 export receptors in the nucleus. Taken together, the current study supports a model in which DRBD18 regulates the selective nuclear export of mRNAs by promoting the mobilization of export competent mRNPs to the cytosol through the nuclear pore complex.
Trvalý link: http://hdl.handle.net/11104/0328946