Dataset Information

MRNA splicing in midbody is essential for proper cell abscission in mitosis

ABSTRACT: Midbody is a transient structure assembled in the last step of mitosis and is currently conceptualized as a structural remnant subject to degradation following cytokinesis. However, our findings indicate that midbody regulation is more complicated than original thought. Knockdown spliceosome proteins in cells showed a multinuclear phenotype and abnormal midbody. Spliceosome and ribosome components are enriched in midbody. We further found that mRNA splicing and protein translation occurs in the midbody during last step of mitosis, which are necessary events for proper abscission of nascent daughter cells. Midbody spliced and translated PRC1 and NINL are essential for proper midbody function. Either PRC1 or NINL knockdown also showed a multinuclear phenotype and abnormal midbody. Treating cancer cells with both chemotherapy and spliceosome inhibitors dramatically lowers the concentration of both drugs, avoiding more severe side effects. Our study discovers a novel regulating mechanism for mitosis and provides a new strategy for cancer therapy.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xiaoyun Liu

PROVIDER: PXD052495 | iProX | Wed May 22 00:00:00 BST 2024

REPOSITORIES: iProX

ACCESS DATA

Similar Datasets

Project description:The proper regulation of RNA processing is critical for muscle development and the fine-tuning of contractile ability among muscle fiber-types. RNA binding proteins (RBPs) regulate the diverse steps in RNA processing including alternative splicing, which generates fiber-type specific isoforms of structural proteins that confer contractile sarcomeres with distinct biomechanical properties. Alternative splicing is disrupted in muscle diseases such as myotonic dystrophy and dilated cardiomyopathy, and is altered after intense exercise as well as with aging. It is therefore important to understand splicing and RBP function, but currently only a small fraction of the hundreds of annotated RBPs expressed in muscle have been characterized. Here we demonstrate the utility of Drosophila as a genetic model system to investigate basic developmental mechanisms of RBP function in myogenesis. We find that RBPs exhibit dynamic temporal and fiber-type specific expression patterns in mRNA-Seq data and display muscle-specific phenotypes. We performed knockdown with 105 RNAi hairpins targeting 35 RBPs and report associated lethality, flight, myofiber and sarcomere defects, including flight muscle phenotypes for Doa, Rm62, mub, mbl, sbr, and clu. Interestingly, knockdown phenotypes of spliceosome components, as highlighted by phenotypes for A-complex components SF1 and Hrb87F (hnRNPA1), revealed level- and temporal-dependent myofibril defects. We further show that splicing mediated by SF1 and Hrb87F is necessary for Z-disc stability and proper myofibril development, and strong knockdown of either gene results in impaired localization of Kettin to the Z-disc. Our results expand the number of RBPs with a described phenotype in muscle and underscore the diversity in myofibril and transcriptomic phenotypes associated with splicing defects. Drosophila is thus a powerful model to gain disease-relevant insight into cellular and molecular phenotypes observed when expression levels of splicing factors, spliceosome components and splicing dynamics are altered.

Dataset Information

MRNA splicing in midbody is essential for proper cell abscission in mitosis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets