Exosome RNA helicase MTR4

Function

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.

Classification

Family (Pfam)

PF00270 DEAD, PF08148 DSHCT, PF00271 Helicase_C, PF21408 MTR4-like_stalk, PF13234 MTR4_beta-barrel

InterPro

Beta-barrel_MTR4, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd, Helicase_C-like, MTR4-like_stalk, P-loop_NTPase, RNA-DNA_Helicase, SKI2-like, Ski2/MTR4_C

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 11

• 6C90 X-ray 2.20A
• 6D6Q EM 3.45A
• 6D6R EM 3.45A
• 6IEG X-ray 3.55A
• 6IEH X-ray 2.89A
• 6RO1 X-ray 3.07A
• 7S7B EM 4.06A
• 7S7C EM 3.62A
• 7Z4Y EM 4.50A
• 7Z4Z EM 4.00A
• 7Z52 EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0071013 catalytic step 2 spliceosome
• GO:0016607 nuclear speck
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0031499 TRAMP complex
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0003723 RNA binding
• GO:0003724 RNA helicase activity
• GO:0006974 DNA damage response
• GO:0000460 maturation of 5.8S rRNA
• GO:0000398 mRNA splicing, via spliceosome
• GO:0006401 RNA catabolic process
• GO:0006364 rRNA processing
• GO:0016076 snRNA catabolic process

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Exosome RNA helicase MTR4 1.00
• ATP-dependent RNA helicase DOB1 0.92
• Circadian oscillator component FRH 0.89
• ATP-dependent RNA helicase mtr4 0.89
• DExH-box ATP-dependent RNA helicase DExH10 0.88
• mRNA transport homolog 4 0.88
• DExH-box ATP-dependent RNA helicase DExH9 0.86
• Circadian oscillator component FRH 0.81
• Circadian oscillator component FRH 0.80
• Uncharacterized helicase C17H9.02 0.77
• U5 small nuclear ribonucleoprotein 200 kDa helicase 0.69
• Putative ATP-dependent RNA helicase C550.03c 0.68

Co-cited proteins · studied together in the literature

• Nuclear valosin-containing protein-like 5 shared papers
• Zinc finger CCHC domain-containing protein 8 6 shared papers
• Nuclear exosome regulator NRDE2 3 shared papers
• WD repeat-containing protein 74 2 shared papers
• RNA-binding protein 7 4 shared papers
• Zinc finger CCHC domain-containing protein 7 2 shared papers
• M-phase phosphoprotein 6 5 shared papers
• Exosome complex component 10 5 shared papers
• Terminal nucleotidyltransferase 4B 2 shared papers
• Nuclear nucleic acid-binding protein C1D 2 shared papers
• Exosome complex component RRP4 4 shared papers
• Serrate RNA effector molecule homolog 1 shared papers

Literature · 30 cited papers

• The MTR4 helicase recruits nuclear adaptors of the human RNA exosome using distinct arch-interacting motifs. Nat. Commun. · 2019
• NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction. Genes Dev. · 2019
• Human nuclear RNAi-defective 2 (NRDE2) is an essential RNA splicing factor. RNA · 2019
• Distinct and evolutionary conserved structural features of the human nuclear exosome complex. Elife · 2018
• Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex. Cell · 2018
• NRDE-2, the human homolog of fission yeast Nrl1, prevents DNA damage accumulation in human cells. RNA Biol. · 2018
• 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
• 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
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors. Nat. Commun. · 2016
• Identification of a nuclear exosome decay pathway for processed transcripts. Mol. Cell · 2016
• AAA-ATPase NVL2 acts on MTR4-exosome complex to dissociate the nucleolar protein WDR74. Biochem. Biophys. Res. Commun. · 2015
• … and 18 more in the literature graph