{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMTR4 is a Ski2-like RNA helicase that acts as a central co‐factor for the nuclear exosome. It functions by bridging the exosome to distinct RNA‐binding adaptor proteins that target specific classes of nuclear RNAs for degradation. For example, MTR4 is part of the NEXT complex that targets early or improperly processed transcripts, and it is also linked via the PAXT connection to process longer, polyadenylated RNAs. In addition, MTR4 is required for efficient rRNA processing by cooperating with adaptor proteins such as MPP6 and C1D, and its depletion leads to the accumulation of unprocessed rRNA precursors and unstable long noncoding RNAs, which disrupt normal RNA homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistically, MTR4’s function is intricately regulated by its interactions with various proteins that both facilitate and restrict its role in exosome recruitment. MTR4 competes with the mRNA export adaptor ALYREF for binding to ARS2, thereby determining whether a transcript is marked for export or degradation. Moreover, aberrant overexpression of MTR4—as observed in hepatocellular carcinoma—can drive metabolic reprogramming by ensuring appropriate alternative splicing of glycolytic genes. Structural studies have revealed that MTR4 recruits adaptors (such as ZCCHC8 and NVL via short linear AIM motifs in its arch domain) and is strategically positioned at the entrance of the RNA channel within the nuclear exosome. In contrast, regulatory proteins such as NRDE2 bind MTR4, locking it in a closed conformation and preventing its association with other recruitment factors, while studies involving TRAMP‐like components indicate that MTR4’s presence is not essential for assembling certain nucleolar RNA surveillance complexes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have broadened the functional landscape of MTR4 by identifying its integration into larger ribonucleoprotein machineries. Its association with factors such as WDR74 has been implicated in the remodeling of ribosomal assembly complexes, while reviews of its structural attributes underscore its versatility in RNA substrate recognition and processing. The zinc‐finger domain of ARS2 is critical for mediating interactions with MTR4 in the poly(A) tail exosome targeting pathway, pointing to coordinated regulation of RNA fate. In infection models, pathogen‐induced alterations result in the loss of MTR4 (and RRP6), leading to nuclear RNA accumulation that impacts host cell physiology. Finally, interactions with splicing regulators like SPF30 and pre‐rRNA processing factors such as PICT1 further link MTR4 to diverse aspects of RNA metabolism and ribosome biogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nicola Meola, Michal Domanski, Evdoxia Karadoulama, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.302604.117"}], "href": "https://doi.org/10.1101/gad.302604.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28733371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28733371"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jing Fan, Bin Kuai, Guifen Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "MTR4 drives liver tumorigenesis by promoting cancer metabolic switch through alternative splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-14437-3"}], "href": "https://doi.org/10.1038/s41467-020-14437-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32024842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32024842"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mahesh Lingaraju, Dennis Johnsen, Andreas Schlundt, et al. 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