ArticleProceedings of the National Academy of Sciences of the United States of America2006
Utilization of host SR protein kinases and RNA-splicing machinery during viral replication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 229 citations in OpenAlex.
- CMGC Kinases in Viral Infection and Human Disease.Pathogens (Basel, Switzerland) · 2026Review
- Utilization of Induced Pluripotent Stem Cell-Derived Neurons to Investigate the Splice-Modification Efficacy of Splice-Switching Drug Candidates.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Acidosis promotes exon skipping through sequestering SR-rich splicing factors in nuclear speckles.Frontiers in molecular biosciences · 2026Article
- Molecular arms races at the virus-host splicing interface and their pathogenic implications.Frontiers in microbiology · 2026Review
- Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing.Science advances · 2025Article
- The splicing factor kinase, SR protein kinase 1 (SRPK1) is essential for late events in the human papillomavirus life cycle.PLoS pathogens · 2025Article
- The Development of Selective Chemical Probes for Serine Arginine Protein Kinase 3.Chemical biology & drug design · 2025Article
- Potential antitumoral effects of SRPK1 inhibition through modulation of VEGF splicing in pituitary somatotroph tumoral cells.Frontiers in endocrinology · 2025Article
- Article
- Compromised CDK12 activity causes dependency on the high activity of O-GlcNAc transferase.Glycobiology · 2024Article
- CDK12-inactivation-induced MYC signaling causes dependency on the splicing kinase SRPK1.Molecular oncology · 2024Article
- NMR analysis, cytotoxic activity and theoretical study of a complex between SRPIN340 andFuture medicinal chemistry · 2024Article
- Design of a covalent protein-protein interaction inhibitor of SRPKs to suppress angiogenesis and invasion of cancer cells.Communications chemistry · 2024Article
- The genetics of resistance to infectious pancreatic necrosis virus in rainbow trout unveiled through survival and virus load data.Frontiers in genetics · 2024Article
- The dual-specificity kinase DYRK1A interacts with the Hepatitis B virus genome and regulates the production of viral RNA.PloS one · 2024Article
- The nexus of long noncoding RNAs, splicing factors, alternative splicing and their modulations.RNA biology · 2024Review
- Article
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- FAM120A couples SREBP-dependent transcription and splicing of lipogenesis enzymes downstream of mTORC1.Molecular cell · 2023Article
- Serine-arginine protein kinases and their targets in viral infection and their inhibition.Cellular and molecular life sciences : CMLS · 2023Review
77 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the viral genome is often quite small, it encodes a broad series of proteins. The virus takes advantage of the host-RNA-processing machinery to provide the alternative splicing capability necessary for the expression of this proteomic diversity. Serine-arginine-rich (SR) proteins and the kinases that activate them are central to this alternative splicing machinery. In studies reported here, we use the HIV genome as a model. We show that HIV expression decreases overall SR protein/activity. However, we also show that HIV expression is significantly increased (20-fold) when one of the SR proteins, SRp75 is phosphorylated by SR protein kinase (SRPK)2. Thus, inhibitors of SRPK2 and perhaps of functionally related kinases, such as SRPK1, could be useful antiviral agents. Here, we develop this hypothesis and show that HIV expression down-regulates SR proteins in Flp-In293 cells, resulting in only low-level HIV expression in these cells. However, increasing SRPK2 function up-regulates HIV expression. In addition, we introduce SR protein phosphorylation inhibitor 340 (SRPIN340), which preferentially inhibits SRPK1 and SRPK2 and down-regulates SRp75. Although an isonicotinamide compound, SPRIN340 (or its derivatives) remain to be optimized for better specificity and lower cytotoxicity, we show here that SRPIN340 suppresses propagation of Sindbis virus in plaque assay and variably suppresses HIV production. Thus, we show that SRPK, a well known kinase in the cellular RNA-processing machinery, is used by at least some viruses for propagation and hence suggest that SRPIN340 or its derivatives may be useful for curbing viral diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.