The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Functional site class:
Rrp6-Rrp47 heterodimer-binding motif in Mtr4
Functional site description:
The exosome complex is involved in degrading or truncating numerous cellular RNA species. In yeast, a ternary complex of the exoribonuclease Rrp6, its cofactor Rrp47, and the Mtr4 helicase binds to the nuclear exosome and enlarges the range of RNA processing capabilities. The interaction between Rrp6-Rrp47 and Mtr4 is mainly due to conserved residues forming a motif near the N-terminus of Mtr4. Rrp6 and Rrp47 build a dimer that provides a binding pocket for Mtr4 at their interface. The recruitment of Mtr4 is determined to only take place in the nucleus.
ELM Description:
The 3’-5’-exoribonuclease Rrp6 (Q12149) makes a tight interaction with Rrp47 (P38801) and the resulting dimer binds directly to the exosomal complex via Rrp6. The heterodimer Rrp6-Rrp47 can then recruit the Mtr4 helicase (P47047) by an N-terminal helical linear motif binding across the dimer interface (4WFD). The surface of the Rrp6/Rrp47 dimer has a concave depression, allowing two turns of amphipathic helix to embed. Using the yeast protein numbering, the Mtr4 motif begins with D5 making a salt bridge to the Rrp47 K84. L6 and F7 then enter the hydrophobic groove. In the second helical turn V9 and F10 enter the hydrophobic groove. Completing the helical motif interaction, E12 forms a salt bridge with R18 of Rrp6.
The current ELM pattern is based on the yeast structure (Schuch,2014) and aligned Mtr4 sequences. It recovers the motif in most animal and fungal Mtr4 proteins. Rarely, the Leu may be substituted by a different hydrophobic residue and, also rarely, the C-terminal negative charge can be absent.
Pattern: [ED]LF[^P][VC]F.{0,1}[ED]
Pattern Probability: 4.761e-08
Present in taxon: Eukaryota
o See 5 Instances for LIG_Rrp6Rrp47_Mtr4_1
o Abstract
The core function of the exosome complex is to cleave RNA molecules. This can either be for RNA processing or RNA destruction purposes. The function of any given exosome complex is individually purposed by the binding of additional proteins and protein complexes: The system is modular. Through the interaction of the Rrp6-Rrp47-Mtr4 complex (Q12149; P38801; P47047) plus Mpp6 (P53725) with exosome complexes, the RNA-processing ability of the nuclear exosome is broadened. Nuclear transcription generates large precursor molecules prior to the mature RNAs. For rRNA, snRNA, and snoRNA maturation, the 3’-end of the precursor molecule needs to be shortened. This process is mainly driven by the exosome itself, a complex of ribonucleases which is also involved in RNA turnover and surveillance of tRNA and mRNA precursors in the nucleus. To ensure that Mtr4 is only able to bind to the exosome within the nucleus, it needs to interact with the heterodimer of two additional nuclear proteins Rrp6 and Rrp47 before being able to attach to the exosome complex (4WFD). In the exosome complex, Mtr4 works as a helicase by unwinding double-stranded segments of the RNA whereas Rrp6 works as an exoribonuclease within the exosome (Schuch,2014). The Rrp6/Rrp47-binding motif appears to be unique to Mtr4. Mtr4 has both Rrp6-dependent and independent functions. It is also a part of the TRAMP complex involved in RNA polyadenylation as well as degradation (Mitchell,2014). The RNA-degrading exosome complex should not be confused with the extracellular vesicles also known as exosomes.
o 4 selected references:

o 5 GO-Terms:

o 5 Instances for LIG_Rrp6Rrp47_Mtr4_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
P42285 MTREX
8 14 ADAFGDELFSVFEGDSTTAA TP 2 Homo sapiens (Human)
Q9Y134 l(2)35Df
5 12 MDIEELFDCFDEVTPSVPPP TP 2 Drosophila melanogaster (Fruit fly)
Q6P7X6 skiv2l2
8 15 ADAFGDDLFSVFDEEQAGSS TP 2 Danio rerio (Zebrafish)
Q1K502 frh
3 10 MDDLFEVFEEQPRAQKKRKA TP 2 Neurospora crassa OR74A
P47047 MTR4
5 12 MDSTDLFDVFEETPVELPTD TP 3 Saccharomyces cerevisiae S288c
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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