lncRNA Malat1 and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation.

lncRNA Malat1 and miR-26 cooperate in the regulation of neuronal progenitor cell proliferation and differentiation.
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DOI:
10.1261/rna.079436.122
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发表时间:
2022-10-27
期刊:
RNA (New York, N.Y.)
影响因子:
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其他
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神经发生是一个精细调节的过程,其依赖于调节细胞分化和增殖的表达程序的平衡执行。从转录因子到染色质调节剂的不同分子参与者控制这些程序。增加了复杂性,非编码(nc)RNA也参与了这一过程。在这里,我们分析了长非编码(lnc)RNA Malat 1在神经胚胎干细胞(ESC)分化过程中的功能。我们发现,Malat 1的缺失导致神经祖细胞(NPC)的增殖抑制。有趣的是,这与分化中的ESC中miR-26家族成员miR-26 a和miR-26 b的表达增加相一致。miR-26 a/B的失活挽救了Malat 1敲除(KO)细胞的增殖表型,并导致化合物Malat 1 KO/mir-26 KO ESC的神经元分化加速。我们的工作共同确定了Malat 1和miR-26在NPC增殖和神经元分化调控中迄今未知的相互作用。
Neurogenesis is a finely tuned process, which depends on the balanced execution of expression programs that regulate cellular differentiation and proliferation. Different molecular players ranging from transcription factors to chromatin modulators control these programs. Adding to the complexity, noncoding (nc)RNAs also take part in this process. Here we analyzed the function of the long noncoding (lnc)RNA Malat1 during neural embryonic stem cell (ESC) differentiation. We find that deletion of Malat1 leads to inhibition of proliferation of neural progenitor cells (NPCs). Interestingly, this coincides with an increase in the expression of miR-26 family members miR-26a and miR-26b in differentiating ESCs. Inactivation of miR-26a/b rescues the proliferative phenotype of Malat1 knockout (KO) cells and leads to accelerated neuronal differentiation of compound Malat1KO/mir-26KO ESCs. Together our work identifies a so far unknown interaction between Malat1 and miR-26 in the regulation of NPC proliferation and neuronal differentiation.
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