Exosome RNA helicase MTR4

Definition:

Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3' RNA extension. Central subunit of many protein complexes, namely TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome targeting (PAXT). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs. PAXT directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor ZCCHC8, which links to RNA-binding protein adapters. Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA. May be involved in pre-mRNA splicing. In the context of NEXT complex can also in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking strand. Can promote unwinding and degradation of structured RNA substrates when associated with the nuclear exosome and its cofactors. Can displace a DNA strand while translocating on RNA to ultimately degrade the RNA within a DNA/RNA heteroduplex. Plays a role in DNA damage response.

References:

[1]. Nicola Meola, et al. Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts. Mol Cell. 2016 Nov 3;64(3):520-533. [Content Brief]

[2]. Michal Lubas, et al. Interaction profiling identifies the human nuclear exosome targeting complex. Mol Cell. 2011 Aug 19;43(4):624-37. [Content Brief]

[3]. Patricia Richard, et al. NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage accumulation in human cells. RNA Biol. 2018;15(7):868-876. [Content Brief]

[4]. Geurt Schilders, et al. C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic Acids Res. 2007;35(8):2564-72. [Content Brief]

[5]. Eva-Maria Weick, et al. Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex. Cell. 2018 Jun 14;173(7):1663-1677.e21. [Content Brief]

[6]. M Rhyan Puno, et al. Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5506-E5515. [Content Brief]

[7]. Nobuhiro Hiraishi, et al. WDR74 participates in an early cleavage of the pre-rRNA processing pathway in cooperation with the nucleolar AAA-ATPase NVL2. Biochem Biophys Res Commun. 2018 Jan 1;495(1):116-123. [Content Brief]

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