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Unique Properties of the Mtr4p−Poly(A) Complex Suggest a Role in Substrate Targeting

机译:Mtr4p-Poly(A)复合物的独特性质表明在底物靶向中的作用

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摘要

Mtr4p is a DEVH-box helicase required for 30n-end processing and degradation of various nuclearnRNA substrates. In particular, Mtr4p is essential for the creation of 5.8S rRNA, U4 snRNA, and somensnoRNAs and for the degradation of cryptic unstable transcripts (CUTs), aberrant mRNAs, and aberrantntRNAs.Many instances of 30n-end processing require limited polyadenylation to proceed.While polyadenylationncan signal degradation in species from bacteria to humans, the mechanism whereby polyadenylatednsubstrates are delivered to the degradation machinery is unknown. Our previous work has shown thatMtr4pnpreferentially binds poly(A) RNA.We suspect that this preference aids in targeting polyadenylated RNAs tonthe exosome. In these studies, we have investigated the mechanism underlying the preference of Mtr4p fornpoly(A) substrates as a means of understanding how Mtr4p might facilitate targeting. Our analysis hasnrevealed that recognition of poly(A) substrates involves sequence-specific changes in the architecture ofnMtr4p-RNA complexes. Furthermore, these differences significantly affect downstream activities. In partic-nular, homopolymeric stretches like poly(A) ineffectively stimulate the ATPase activity ofMtr4p and suppressnthe rate of dissociation of theMtr4p-RNA complex. These findings indicate that theMtr4p-poly(A) complex isnunique and ideally suited for targeting key substrates to the exosome.
机译:Mtr4p是DEVH-box解旋酶,是30n末端加工和降解各种nuclearnRNA底物所需的。尤其是Mtr4p对于5.8S rRNA,U4 snRNA和somensnoRNA的创建以及隐性不稳定转录本(CUT),异常mRNA和异常RNA的降解至关重要。许多30n末端加工需要有限的多腺苷酸化才能进行。尽管聚腺苷酸化可以信号指示细菌从细菌到人类的降解过程,但将聚腺苷酸化的底物传递至降解机制的机制尚不清楚。我们以前的工作表明,Mtr4pn优先结合poly(A)RNA。我们怀疑这种偏好有助于靶向外来体的聚腺苷酸化RNA。在这些研究中,我们研究了Mtr4p fornpoly(A)底物偏爱的潜在机制,以此作为了解Mtr4p如何促进靶向的手段。我们的分析表明,poly(A)底物的识别涉及nMtr4p-RNA复合物结构的序列特异性变化。此外,这些差异显着影响下游活动。在特定的区域中,均聚物拉伸片段(如poly(A))不能有效地刺激Mtr4p的ATPase活性,并抑制Mtr4p-RNA复合物的解离速率。这些发现表明,Mtr4p-poly(A)复合物是独特的,非常适合将关键底物靶向外泌体。

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