期刊
EMBO JOURNAL
卷 41, 期 13, 页码 -出版社
WILEY
DOI: 10.15252/embj.2021108918
关键词
competing endogenous RNA; long noncoding RNAs; microRNAs; motor neuron differentiation; single-cell RNA sequencing
资金
- ERC [855923-ASTRA]
- AIRC [23053, IG18774, IG22851]
- EC [721890]
- PRIN [2017P352Z4]
- H2020 Program Sapienza Progetti Collaborativi
- Sapienza University [RM12117A5DE7A45B, RM11916B7A39DCE5]
- POR FESR Lazio [2020-T0002E0001]
- Fondazione Cariplo [2015-0590, 2016-0615]
- Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement
- Marie Curie Actions (MSCA) [721890] Funding Source: Marie Curie Actions (MSCA)
The transition from dividing progenitors to postmitotic motor neurons (MNs) is regulated by a MN-specific transcriptional unit (MN2), which contains a long non-coding RNA (lncMN2-203) and two microRNAs (miR-325-3p and miR-384-5p). The lncMN2-203 affects MN differentiation by upregulating miR-466i-5p targets, while miR-325-3p and miR-384-5p repress proliferation-related factors. This study demonstrates the importance of post-transcriptional regulation in MN differentiation.
The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post-transcriptional role of a MN-specific transcriptional unit (MN2) harboring a lncRNA (lncMN2-203) and two miRNAs (miR-325-3p and miR-384-5p) in this transition. Through the use of in vitro mESC differentiation and single-cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2-203 affects MN differentiation by sponging miR-466i-5p and upregulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR-325-3p and miR-384-5p, co-transcribed with lncMN2-203, act by repressing proliferation-related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation.
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