PUBLICATION
linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells
- Authors
- Tornini, V.A., Miao, L., Lee, H.J., Gerson, T., Dube, S.E., Schmidt, V., Kroll, F., Tang, Y., Du, K., Kuchroo, M., Vejnar, C.E., Bazzini, A.A., Krishnaswamy, S., Rihel, J., Giraldez, A.J.
- ID
- ZDB-PUB-230516-55
- Date
- 2023
- Source
- eLIFE 12: (Journal)
- Registered Authors
- Giraldez, Antonio, Rihel, Jason, Tornini, Valerie A., Vejnar, Charles
- Keywords
- behavior, cell identity, developmental biology, gene regulation, micropeptides, neurodevelopment, neuroscience, single cell analyses, zebrafish
- Datasets
- GEO:GSE228551
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Chromatin
- Humans
- RNA, Long Noncoding*/genetics
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 37191016 Full text @ Elife
Citation
Tornini, V.A., Miao, L., Lee, H.J., Gerson, T., Dube, S.E., Schmidt, V., Kroll, F., Tang, Y., Du, K., Kuchroo, M., Vejnar, C.E., Bazzini, A.A., Krishnaswamy, S., Rihel, J., Giraldez, A.J. (2023) linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells. eLIFE. 12:.
Abstract
Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open-reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here, we show that two putative lincRNAs (linc-mipep, also called lnc-rps25, and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings reveal a key missing link in the evolution of vertebrate brain cell development and illustrate a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping