Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei.
Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei.
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DRBD18促进布氏锥虫mRNA选择性核输出
DOI：
10.1111/mmi.14773
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发表时间：
2021-09
影响因子：
3.6
通讯作者：
Read LK
中科院分区：
文献类型：
--
作者：
Mishra A;Kaur JN;McSkimming DI;Hegedűsová E;Dubey AP;Ciganda M;Paris Z;Read LK
动质体（包括布氏锥虫）主要在转录后水平调控基因表达。核mRNA输出是该过程中一个重要但研究不足的步骤。通用的异二聚体输出因子Mex67/Mtr2在布氏锥虫的mRNA和tRNA输出中起作用，但通过控制Mex67/Mtr2核糖核蛋白形成或运输的动态来调节输出过程的RNA结合蛋白（RBP）尚未被确定。在此，我们报道DRBD18这种布氏锥虫必需且大量存在的RBP在体内与Mex67/Mtr2相关联，可能是通过其与Mtr2的直接相互作用。DRBD18的下调导致多聚腺苷酸（poly(A)+）mRNA在核内部分积累，但对含内含子或成熟tRNA的定位没有影响。对DRBD18敲低的寄生虫全细胞和细胞质转录组的综合分析表明，DRBD18的缺失导致一部分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的敲低导致Mex67/Mtr2输出受体在核内部分积累。综上所述，当前的研究支持一种模型，即DRBD18通过促进有输出能力的mRNA核糖核蛋白复合物通过核孔复合体向细胞质的动员来调节mRNA的选择性核输出。
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 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 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.
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影响因子：
56.9
作者：
Kolev, Nikolay G.;Ramey-Butler, Kiantra;Tschudi, Christian
通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
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影响因子：
3.7
作者：
Klein C;Terrao M;Inchaustegui Gil D;Clayton C
通讯作者：
Clayton C