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Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-06-19 , DOI: 10.1111/mmi.14773
Amartya Mishra 1 , Jan Naseer Kaur 1 , Daniel I McSkimming 2 , Eva Hegedűsová 3 , Ashutosh P Dubey 1 , Martin Ciganda 1 , Zdeněk Paris 3, 4 , Laurie K Read 1
Affiliation  

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.

中文翻译:

DRBD18 在布氏锥虫中促进 mRNA 的选择性核输出

动质体,包括布氏锥虫,主要在转录后水平控制基因表达。核 mRNA 输出是这一过程中一个重要但未被充分研究的步骤。一般异二聚体输出因子 Mex67/Mtr2 在T. brucei中的 mRNA 和 tRNA 输出中起作用,但通过控制 Mex67/Mtr2 核糖核蛋白形成或转运的动力学来调节输出过程的 RNA 结合蛋白 (RBP) 尚未确定. 在这里,我们报告 DRBD18 是一种必需且丰富的T. brucei RBP,可能通过其与 Mtr2 的直接相互作用在体内与 Mex67/Mtr2 相关联。DRBD18 下调导致 poly(A) +的部分积累mRNA 在细胞核中,但对含内含子或成熟 tRNA 的定位没有影响。对 DRBD18 敲低寄生虫中全细胞和胞质溶胶的转录组的综合分析表明,DRBD18 的消耗会导致一部分 mRNA 的核输出受损。CLIP 实验揭示了 DRBD18 与其中几种 mRNA 的关联。此外,DRBD18 敲低导致细胞核中 Mex67/Mtr2 输出受体的部分积累。总之,目前的研究支持一个模型,其中 DRBD18 通过促进输出能力的 mRNPs 通过核孔复合物向胞质溶胶的动员来调节 mRNAs 的选择性核输出。
更新日期:2021-06-19
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