A CDK-11/SAP30BP/CYL-1 Complex Links Pre-mRNA Splicing to Developmental Cell Fate Decisions

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The paper investigates the in vivo roles of the cyclin-like protein CYL-1 and its interacting partners during Caenorhabditis elegans development, focusing on how CYL-1 links pre-mRNA splicing to developmental fate decisions. CYL-1 was found to be ubiquitously expressed in cell nuclei throughout development; coimmunoprecipitation followed by mass spectrometry identified complexes containing CDK-11.1, CDK-11.2, and EEOL-1, and genetic analyses showed these four proteins are essential for mRNA biogenesis, with CDK-11.1 and CDK-11.2 functioning redundantly for embryonic viability. Immunostaining indicated CYL-1 is required for transcriptional initiation and elongation, and a cell fate marker demonstrated roles for CDK-11.1, CDK-11.2, and EEOL-1 in cell fate specification, with the main limitation being that the work is presented as an unreviewed preprint. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Background Cyclin-dependent kinases (CDKs) and cyclins are integral to regulating cell cycle progression; however, many have additional roles in metazoans beyond controlling the cell cycle. One such cyclin, Cyclin L (CYL-1), has been shown to participate in pre-mRNA splicing through its interaction with CDK-11 in various cell lines. However, the in vivo functions of CYL-1 and its interacting partners during animal development remain poorly understood. Results In this study, we investigated the developmental roles of CYL-1 in Caenorhabditis elegans. Our findings revealed that CYL-1 is ubiquitously expressed in cell nuclei throughout development. By performing coimmunoprecipitation followed by mass spectrometry, we identified its interacting partners, confirming that CYL-1 forms complexes with both CDK-11.1 and CDK-11.2, as well as the highly conserved protein EEOL-1. Genetic analyses indicate that these four proteins are essential for mRNA biogenesis, with CDK-11.1 and CDK-11.2 functioning redundantly to regulate embryonic viability. Immunostaining assays demonstrated that CYL-1 plays a crucial role in both transcriptional initiation and elongation. Furthermore, using a cell fate marker, we demonstrated that CDK-11.1, CDK-11.2, and EEOL-1 are also involved in regulating cell fate specification. Conclusions Collectively, our findings establish that CYL-1 forms a complex with CDK-11.1, CDK-11.2, and EEOL-1, orchestrating mRNA biogenesis and cell fate determination during development. This research not only enhances our understanding of the multifaceted roles of CYL-1 but also sheds light on the intricate regulatory networks governing developmental processes.
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A CDK-11/SAP30BP/CYL-1 Complex Links Pre-mRNA Splicing to Developmental Cell Fate Decisions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A CDK-11/SAP30BP/CYL-1 Complex Links Pre-mRNA Splicing to Developmental Cell Fate Decisions Lu-Yan Chan, Ming-Kin Wong, Wen-Jun Li, Vincy Wing Sze Ho, Yiming Ma, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7629361/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Cyclin-dependent kinases (CDKs) and cyclins are integral to regulating cell cycle progression; however, many have additional roles in metazoans beyond controlling the cell cycle. One such cyclin, Cyclin L (CYL-1), has been shown to participate in pre-mRNA splicing through its interaction with CDK-11 in various cell lines. However, the in vivo functions of CYL-1 and its interacting partners during animal development remain poorly understood. Results In this study, we investigated the developmental roles of CYL-1 in Caenorhabditis elegans. Our findings revealed that CYL-1 is ubiquitously expressed in cell nuclei throughout development. By performing coimmunoprecipitation followed by mass spectrometry, we identified its interacting partners, confirming that CYL-1 forms complexes with both CDK-11.1 and CDK-11.2, as well as the highly conserved protein EEOL-1. Genetic analyses indicate that these four proteins are essential for mRNA biogenesis, with CDK-11.1 and CDK-11.2 functioning redundantly to regulate embryonic viability. Immunostaining assays demonstrated that CYL-1 plays a crucial role in both transcriptional initiation and elongation. Furthermore, using a cell fate marker, we demonstrated that CDK-11.1, CDK-11.2, and EEOL-1 are also involved in regulating cell fate specification. Conclusions Collectively, our findings establish that CYL-1 forms a complex with CDK-11.1, CDK-11.2, and EEOL-1, orchestrating mRNA biogenesis and cell fate determination during development. This research not only enhances our understanding of the multifaceted roles of CYL-1 but also sheds light on the intricate regulatory networks governing developmental processes. CYL-1 mRNA biogenesis CDK-11 cell fate differentiation C. elegans Full Text Additional Declarations No competing interests reported. Supplementary Files TableS1.xlsx TableS2.xlsx TableS3.xlsx TableS4.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Dec, 2025 Reviews received at journal 31 Oct, 2025 Reviews received at journal 27 Oct, 2025 Reviewers agreed at journal 08 Oct, 2025 Reviewers agreed at journal 08 Oct, 2025 Reviewers invited by journal 24 Sep, 2025 Editor assigned by journal 17 Sep, 2025 Submission checks completed at journal 17 Sep, 2025 First submitted to journal 16 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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