Regulation of DEAH-box RNA helicases by G-patch proteins

Abstract

RNA helicases of the DEAH/RHA family form a large and conserved class of enzymes that remodel RNA protein complexes (RNPs) by translocating along the RNA. Driven by ATP hydrolysis, they exert force to dissociate hybridized RNAs, dislocate bound proteins or unwind secondary structure elements in RNAs. The sub-cellular localization of DEAH-helicases and their concomitant association with different pathways in RNA metabolism, such as pre-mRNA splicing or ribosome biogenesis, can be guided by cofactor proteins that specifically recruit and simultaneously activate them. Here we review the mode of action of a large class of DEAH-specific adaptor proteins of the G-patch family. Defined only by their eponymous short glycine-rich motif, which is sufficient for helicase binding and stimulation, this family encompasses an immensely varied array of domain compositions and is linked to an equally diverse set of functions. G-patch proteins are conserved throughout eukaryotes and are even encoded within retroviruses. They are involved in mRNA, rRNA and snoRNA maturation, telomere maintenance and the innate immune response. Only recently was the structural and mechanistic basis for their helicase enhancing activity determined. We summarize the molecular and functional details of G-patch-mediated helicase regulation in their associated pathways and their involvement in human diseases.

A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation

“…The activity of DEAH RNA helicases, such as DHX34, is often regulated through G-patch proteins, which function as adaptors that recruit them to functional sites and enhance their activity (Studer et al 2020). The G-patch domain is an intrinsically unstructured region containing a set of conserved glycines that interact with an auxiliary OB-fold (oligonucleotide/oligosaccharide-binding fold) of their cognate DEAH box helicase and mediate protein-protein and RNA-protein interactions (Bohnsack et al 2021; Robert-paganin et al 2015; Studer et al 2020). The interactome of DHX34 in HEK293T cells revealed the presence of one such protein, GPATCH1 (Fig.…”

Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis

“…Then, we conducted AS analysis since the domains SURP1/2 and G-patch always participated in the AS process. Alternative splicing, by which pre-mRNA molecules can be spliced in different ways to generate multiple mRNA isoforms from a single gene, is the main mechanism of transcriptome and proteome expansion that can explain the phenotypic complexity of organisms and tissues (29)(30)(31). In the five main AS events, Sugp2 mainly regulated the skip of exons which would probably generate abnormal exon-skipped transcripts with a premature termination codon.…”

RNA folding and functions of RNA helicases in ribosome biogenesis

“…It unwinds RNA duplexes with a 3’ overhang much more efficiently than duplexes with a 5’ overhang, indicating that Prp43 displays 3’ to 5’ directionality [ 219 ]. The function of Prp43 is regulated by a group of co-factors termed G-patch proteins (reviewed in more detail in [ 220 , 221 ]). So far, four different G-patch co-factors of Prp43 have been identified: Ntr1/Spp382, Pxr1/Gno1, Pfa1/Sqs1, and Cmg1.…”

“…The extended conformation provides sufficient flexibility to allow for RecA domain movements required for substrate processing. The mechanism of activation is believed to be by tethering the RecA2 and WH domains together via the brace-like G-patch domain, thereby keeping the RNA channel in a closed, RNA bound conformation, and consequently increasing processivity of the helicase [ 220 , 235 ].…”