Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing.

Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing.
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DOI:
10.1093/nar/gkv005
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发表时间:
2015-02-18
影响因子:
14.9
通讯作者:
van Hoof A
van Hoof A
中科院分区:
生物学2区
文献类型:
--
作者:
Losh JS;King AK;Bakelar J;Taylor L;Loomis J;Rosenzweig JA;Johnson SJ;van Hoof A

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RNA外泌体是真核细胞中主要的3′ ~ 5′核糖核酸外切酶之一。虽然它负责降解或加工各种底物RNA,但它非常特异,可以区分底物和非底物RNA以及需要3′加工的底物和需要完全降解的底物。这种特异性似乎不是由外泌体本身决定的,而是由十几种其他蛋白质决定的。这些外泌体辅因子中有四种具有酶活性,即核RNA依赖性ATP酶Mtr 4、其细胞质旁系同源物Ski 2以及核非典型多聚腺苷酸聚合酶Trf 4和Trf 5。Mtr 4和Trf 4或Trf 5组装成TRAMP复合物。然而,这些酶如何组装成TRAMP复合物以及TRAMP复合物组装的功能后果仍然未知。在这里,我们确定了Mtr 4和Trf 5之间的一个重要的相互作用位点,并表明破坏Mtr 4/Trf相互作用会破坏特定的TRAMP和外泌体功能,包括snoRNA加工。
The RNA exosome is one of the main 3′ to 5′ exoribonucleases in eukaryotic cells. Although it is responsible for degradation or processing of a wide variety of substrate RNAs, it is very specific and distinguishes between substrate and non-substrate RNAs as well as between substrates that need to be 3′ processed and those that need to be completely degraded. This specificity does not appear to be determined by the exosome itself but rather by about a dozen other proteins. Four of these exosome cofactors have enzymatic activity, namely, the nuclear RNA-dependent ATPase Mtr4, its cytoplasmic paralog Ski2 and the nuclear non-canonical poly(A) polymerases, Trf4 and Trf5. Mtr4 and either Trf4 or Trf5 assemble into a TRAMP complex. However, how these enzymes assemble into a TRAMP complex and the functional consequences of TRAMP complex assembly remain unknown. Here, we identify an important interaction site between Mtr4 and Trf5, and show that disrupting the Mtr4/Trf interaction disrupts specific TRAMP and exosome functions, including snoRNA processing.
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