RNA-Binding Proteins in mRNA Splicing: Orchestration of Altered Phosphorylation of RNA-Binding Domains via Kinase Regulatory Networks
- 1Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University), Mangalore 575018, India
Abstract
RNA-binding proteins (RBPs) are crucial regulators of post-transcriptional gene expression, orchestrating essential processes including splicing, mRNA transport, translation modulation, and mRNA decay. Phosphorylation of RBPs is crucial for regulatory mechanisms, mediating how extracellular stimuli control intracellular signaling and cellular decisions. In this study, mass spectrometry-based phosphoproteomic data were systematically integrated and harmonized, and Fisher’s exact test (p-Value < 0.05) was applied to quantify conserved co-differential phosphorylation across pairs of phosphorylation sites in comparison to a chosen set of RNA-binding proteins (HNRNPM, SLU7, and SRSF5). For each such pair, data were benchmarked across >800 phosphorylation profiling and 200 differential phosphorylation datasets, identifying predominant co-differential phosphorylation patterns that accounted for >75% of all observed phosphorylation events. Major phosphorylation hotspots were identified in HNRNPM, SLU7, and SRSF5 RNA-binding proteins. High-confidence pairs were further refined using secondary filters, yielding a focused set of functionally relevant relationships in mRNA and alternative splicing. As the RNA-binding activity is mediated by RNA-binding proteins (RBDs), co-differentially regulated phosphorylation sites were mapped to RBDs, and upstream kinases modulating such phosphorylation were derived from experimental, semi-experimental and predictive sources. Overall analysis confirmed phosphorylation of RBPs on their RBDs through the upstream kinases, modulating mRNA and alternative splicing through a conserved network of co-differential phosphorylation events. With further validation, the data imply a platform for identifying relevant targets and markers for studying mRNA splicing and RNA-binding activity, central to RNA processing.
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BibTeX
@article{bangera2026rnabinding,
title = {{RNA-Binding Proteins in mRNA Splicing: Orchestration of Altered Phosphorylation of RNA-Binding Domains via Kinase Regulatory Networks}},
author = {Ashika Bangera and Samseera Ummar and Alimath Sambreena and Athira Perunelly Gopalakrishnan and Poornima Ramesh and Rajesh Raju},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219965},
url = {https://www.mdpi.com/1422-0067/27/21/9965},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RNA-Binding Proteins in mRNA Splicing: Orchestration of Altered Phosphorylation of RNA-Binding Domains via Kinase Regulatory Networks
AU - Ashika Bangera
AU - Samseera Ummar
AU - Alimath Sambreena
AU - Athira Perunelly Gopalakrishnan
AU - Poornima Ramesh
AU - Rajesh Raju
PY - 2026
DA - 2026/11/06
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219965
UR - https://www.mdpi.com/1422-0067/27/21/9965
AB - RNA-binding proteins (RBPs) are crucial regulators of post-transcriptional gene expression, orchestrating essential processes including splicing, mRNA transport, translation modulation, and mRNA decay. Phosphorylation of RBPs is crucial for regulatory mechanisms, mediating how extracellular stimuli control intracellular signaling and cellular decisions. In this study, mass spectrometry-based phosphoproteomic data were systematically integrated and harmonized, and Fisher’s exact test (p-Value < 0.05) was applied to quantify conserved co-differential phosphorylation across pairs of phosphorylation sites in comparison to a chosen set of RNA-binding proteins (HNRNPM, SLU7, and SRSF5). For each such pair, data were benchmarked across >800 phosphorylation profiling and 200 differential phosphorylation datasets, identifying predominant co-differential phosphorylation patterns that accounted for >75% of all observed phosphorylation events. Major phosphorylation hotspots were identified in HNRNPM, SLU7, and SRSF5 RNA-binding proteins. High-confidence pairs were further refined using secondary filters, yielding a focused set of functionally relevant relationships in mRNA and alternative splicing. As the RNA-binding activity is mediated by RNA-binding proteins (RBDs), co-differentially regulated phosphorylation sites were mapped to RBDs, and upstream kinases modulating such phosphorylation were derived from experimental, semi-experimental and predictive sources. Overall analysis confirmed phosphorylation of RBPs on their RBDs through the upstream kinases, modulating mRNA and alternative splicing through a conserved network of co-differential phosphorylation events. With further validation, the data imply a platform for identifying relevant targets and markers for studying mRNA splicing and RNA-binding activity, central to RNA processing.
SN - 1422-0067
ER -