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IFIT proteins (interferon-induced proteins with tetratricopeptide repeats) are key components of the innate immune response that bind to viral and cellular RNA targets to inhibit viral translation and replication. The RNA target recognition is guided by molecular patterns, particularly at the RNA 5' ends. IFIT1 preferably binds RNAs modified with the 7-methylguanosine (m7G) cap-0 structure, while RNAs with cap-1 structure are recognized with lower affinity.
View Article and Find Full Text PDFThe mRNA cap methyltransferase CMTR1 plays a crucial role in RNA metabolism and gene expression regulation, yet its significance in cancer remains largely unexplored. Here, we present a comprehensive multi-omics analysis of CMTR1 across various human cancers, revealing its widespread upregulation and potential as a therapeutic target. Integrating transcriptomic and proteomic data from a large set of cancer samples, we demonstrate that CMTR1 is upregulated at the mRNA, protein, and phosphoprotein levels across multiple cancer types.
View Article and Find Full Text PDFConcise Affinity-Based Purification of Ligated mRNA for Structure-Activity Relationship Studies of Nucleosugar Modification Patterns.
Chembiochem
November 2024
Modality Research Laboratories 1, Research Unit, Research Division, Kyowa Kirin Co., Ltd., 3-6-6 Asahi, Machida, Tokyo, 194-8533, Japan.
Position-specific nucleoside sugar modifications have been shown to improve the translational activity and stability of chemically synthesized mRNA. For pharmaceutical applications of chemically modified mRNAs, a rapid purification methodology is imperative to identify the optimal modification pattern. However, while the chemical synthesis of mRNAs can be accomplished by splint ligation of oligonucleotide fragments, the current purification method for ligated mRNAs based on denaturing polyacrylamide gel electrophoresis tends to be time consuming.
View Article and Find Full Text PDFLARP1 binds ribosomes and TOP mRNAs in repressed complexes.
EMBO J
December 2024
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in 40S- or 80S-ribosome complexes that are thought to repress and stabilize TOPs. However, a molecular understanding of how LARP1 and TOPs interact with these ribosome complexes is lacking.
View Article and Find Full Text PDFRHPS4 Targeted the G-Quadruplex of the Gene of to Inhibit Viral Proliferation.
J Agric Food Chem
November 2024
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
Small molecules targeting G-quadruplexes (G4s) in viruses could inhibit viral proliferation. The 1a protein of (CMV) act as RNA-dependent RNA polymerase (RdRp) that plays a crucial role in regulating the replication of CMV. In this study, four putative G4 sequences (CMV PQS1-PQS4) in the genetic coding region of CMV were identified, and three of them (PQS2, PQS3, and PQS4) were confirmed to fold into G4 structures.
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