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ABSTRACT miR-31 is a highly conserved microRNA that plays crucial roles in cell proliferation, migration and differentiation. We discovered that miR-31 and some of its validated targets are enriched on the mitotic spindle of the dividing sea urchin embryo and mammalian cells. Using the sea urchin embryo, we found that miR-31 inhibition led to developmental delay correlated with increased cytoskeletal and chromosomal defects. We identified miR-31 to directly suppress several actin remodeling transcripts, including β-actin, Gelsolin, Rab35 and Fascin. De novo translation of Fascin occurs at the mitotic spindle of sea urchin embryos and mammalian cells. Importantly, miR-31 inhibition leads to a significant a increase of newly translated Fascin at the spindle of dividing sea urchin embryos. Forced ectopic localization of Fascin transcripts to the cell membrane and translation led to significant developmental and chromosomal segregation defects, highlighting the importance of the regulation of local translation by miR-31 at the mitotic spindle to ensure proper cell division. Furthermore, miR-31-mediated post-transcriptional regulation at the mitotic spindle may be an evolutionarily conserved regulatory paradigm of mitosis.
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microRNA‐124 regulates Notch and NeuroD1 to mediate transition states of neuronal development
Abstract MicroRNAs regulate gene expression by destabilizing target mRNA and/or inhibiting translation in animal cells. The ability to mechanistically dissect miR‐124′s function during specification, differentiation, and maturation of neurons during development within a single system has not been accomplished. Using the sea urchin embryo, we take advantage of the manipulability of the embryo and its well‐documented gene regulatory networks (GRNs). We incorporatedNeuroD1as part of the sea urchin neuronal GRN and determined that miR‐124 inhibition resulted in aberrant gut contractions, swimming velocity, and neuronal development. Inhibition of miR‐124 resulted in an increased number of cells expressing transcription factors (TFs) associated with progenitor neurons and a concurrent decrease of mature and functional neurons. Results revealed that in the early blastula/gastrula stages, miR‐124 regulates undefined factors during neuronal specification and differentiation. In the late gastrula/larval stages, miR‐124 regulatesNotchandNeuroD1during the transition between neuronal differentiation and maturation. Overall, we have improved the neuronal GRN and identified miR‐124 to play a prolific role in regulating various transitions of neuronal development.
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- Award ID(s):
- 2103453
- PAR ID:
- 10402702
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Developmental Neurobiology
- Volume:
- 83
- Issue:
- 1-2
- ISSN:
- 1932-8451
- Page Range / eLocation ID:
- p. 3-27
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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