Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors

Kretova, Miroslava; Selicky, Tomas; Cipakova, Ingrid; Čipák, Luboš

doi:10.3390/life13030604

Cited by 11 publications

(9 citation statements)

References 331 publications

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“…Yet, despite the limitation in individual PTM annotation, larger patterns between splicing and PTM-driven regulation still emerge. It has previously been suggested that transcription and alternative splicing are functionally coupled [46], and the activity of many splicing factors are regulated by post-translational modifications to induce splicing changes [47]. Examples of potential signaling-transcription-splicing cross-talk exist throughout literature, such as HRAS-mutant dependent splicing via SRSF proteins in lung cancer [48] and combined control of NF- κ B signaling by splicing and PTMs [49].…”

Section: Discussionmentioning

confidence: 99%

A systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms

Crowl,

Coleman,

Chaphiv

et al. 2024

Preprint

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Post-translational modifications (PTMs) and splicing are known to be important regulatory processes for controlling protein function and activity. However, there have been limitations in analyzing the interplay of alternative splicing and PTMs, both from the standpoint of PTM presence and in the possible diversification of the regulatory windows of PTMs, which define the connection to regulatory enzymes and possible binding partners. Limitations stem from the deep differences in genomic and proteomic databases, where PTMs are predominantly identified by mass spectrometry and subsequently assigned to the canonical isoform of the protein in databases. In this work, we bridge the protein- and genome-centric world views to map PTMs to genomic locations for subsequent projection of PTMs onto alternative isoforms. We then perform a systematic analysis of the diversification of PTMs within all defined protein isoforms, focusing on the PTM-specific profiles that may differ across the various major modifications found in humans, including exploration of how often alternative splicing leads to diversification of the regulatory sequences directly flanking a PTM. We found the interplay between splicing and PTMs is PTM-specific across a range of behaviors, such as PTM inclusion rates across isoforms and tissues. Additionally we found that ~2% of prospective PTM sites exhibited altered regulatory sequences surrounding the modification site, suggesting that regulatory or binding interactions might be diversified in these proteoforms. In addition to exploring isoforms as defined by Ensembl, we applied this PTM-to-isoform mapping approach to explore the impacts of disease-related splicing in prostate cancer, identifying possible new hypotheses as to the variable mechanisms of ESRP1 expression in different cancers.

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Section: Discussionmentioning

confidence: 99%

A systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms

Crowl,

Coleman,

Chaphiv

et al. 2024

Preprint

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show abstract

“…Specifically, after transcription, mRNA precursors contain introns and exons. Non-coding intronic sequences are excised, and exons are joined by a macromolecular complex-the spliceosome [44]. Following this, ribosomes recognize the codons on mRNA and, with the assistance of the appropriate tRNA molecules, synthesize proteins [45].…”

Section: Discussionmentioning

confidence: 99%

White Isthmus Transcriptome Analysis Reveals the Mechanism of Translucent Eggshell Formation

Ma,

Luo,

et al. 2024

Animals

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The presence of translucent eggshells is a type of egg quality issue that impacts egg sales. While many researchers have studied them, the exact mechanisms behind their formation remain unclear. In this study, we conducted a transcriptomic differential expression analysis of the isthmus region of the oviduct in both normal egg- and translucent egg-laying hens. The analysis revealed that differentially expressed gene pathways were predominantly concentrated in the synthesis, modification, and transport of eggshell membrane proteins, particularly collagen proteins, which provide structural support. These findings suggest that variations in the physical structure of the eggshell membrane, resulting from changes in its chemical composition, are the fundamental cause of translucent eggshell formation. This research provides a theoretical reference for reducing the occurrence of translucent eggs.

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“…The mutant variants engineered in this study could serve in complementation assays of the sr45-1 mutant with both SR45 isoforms using native promoter-driven translational fusions. Moreover, it was shown that acetylation, methylation, SUMOylation, ubiquitylation, or even prolyl cis-trans isomerization can regulate the activity of animal SR proteins and other splicing factors (Slišković et al ., 2022; Kretova et al ., 2023). Therefore, dissecting more precisely each of the SR45 isoform domains and focusing on all types of post-translational modifications would demonstrate the importance of specific residues associated to the molecular function of SR45 and to its physiological responses in the plant.…”

Section: Discussionmentioning

confidence: 99%

TheArabidopsisSR45 splicing factor bridges the splicing machinery and the exon-exon junction complex

Fanara,

Schloesser,

Joris

et al. 2023

Preprint

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The Arabidopsis splicing factor serine/arginine-rich 45 (SR45) contributes to several biological processes. The sr45-1 loss-of-function mutant exhibits delayed root development, late flowering, unusual numbers of floral organs, shorter siliques with decreased seed sets, narrower leaves and petals, and altered metal distribution. Here, we studied the function of each of SR45 domains by examining their involvement in: (i) the spatial distribution of SR45, (ii) the establishment of a protein-protein interaction network including spliceosomal and exon-exon junction complex (EJC) components, and (iii) the RNA binding specificity. We report that the endogenous SR45 promoter is active during vegetative and reproductive growth, and that the SR45 protein localizes in the nucleus. We demonstrate that the C-terminal arginine/serine-rich domain is a determinant of nuclear localization. We show that the SR45 RNA recognition motif (RRM) domain specifically binds purine-rich RNA motifs via three residues (H101, H141, Y143), and is also involved in protein-protein interactions. We further show that SR45 bridges both mRNA splicing and surveillance machineries as a partner of EJC core components and peripheral factors, which requires phosphoresidues likely phosphorylated by kinases from both CLK and SRPK families. Our findings provide insights into the contribution of each SR45 domain to both spliceosome and EJC assemblies.

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Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors

Cited by 11 publications

References 331 publications

A systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms

A systematic analysis of the effects of splicing on the diversity of post-translational modifications in protein isoforms

White Isthmus Transcriptome Analysis Reveals the Mechanism of Translucent Eggshell Formation

TheArabidopsisSR45 splicing factor bridges the splicing machinery and the exon-exon junction complex

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