Sequential and additive expression of miR-9 precursors control timing of neurogenesis.
Sequential and additive expression of miR-9 precursors control timing of neurogenesis.
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DOI：
10.1242/dev.200474
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发表时间：
2022-10-01
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影响因子：
--
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--
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microRNA（miRs）在调节动态基因表达中具有重要作用。然而，它们被定量控制的机制是未知的。我们发现，成熟的miR-9，神经元发育的关键调节因子，在斑马鱼神经发生过程中以一种急剧的逐步方式增加。我们描述了7种不同的microRNA初级转录物（pri-mir）-9的时空分布，这些转录物产生相同的成熟miR-9，并表明它们在后脑神经发生过程中顺序表达。晚发型pri-mir-9-1的表达被添加到单细胞中的早发型pri-mir-9-4和-9-5的表达上，而不是替换。晚发型pri-mir-9-1的CRISPR/Cas9突变阻止成熟miR-9的发育增加，减少晚期神经元分化，并且未能在晚期下调Her 6。数学建模表明，含有Her 6的自适应网络对miR-9的线性增加不敏感，但对miR-9的逐步增加有反应。我们认为，成熟的miR-9的急剧逐步增加是由不同位点的顺序和附加的时间激活产生的。这可能是克服适应并促进Her 6向新的动态状态或稳态转变的策略。 成熟miR-9的急剧逐步增加是由不同基因座的顺序-时间激活促成的;这是一种克服适应并促进向Her 6动力学/水平的新状态过渡的策略。
MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state. Sharp stepwise increase of mature miR-9 is contributed by sequential-temporal activation of distinct loci; a strategy to overcome adaptation and facilitate a transition to a new state of Her6 dynamics/level.
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影响因子：
10.5
作者：
Chen, PY;Manninga, H;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
16.6
作者：
Berthelot, Camille;Brunet, Frederic;Chalopin, Domitille;Juanchich, Amelie;Bernard, Maria;Noel, Benjamin;Bento, Pascal;Da Silva, Corinne;Labadie, Karine;Alberti, Adriana;Aury, Jean-Marc;Louis, Alexandra;Dehais, Patrice;Bardou, Philippe;Montfort, Jerome;Klopp, Christophe;Cabau, Cedric;Gaspin, Christine;Thorgaard, Gary H.;Boussaha, Mekki;Quillet, Edwige;Guyomard, Rene;Galiana, Delphine;Bobe, Julien;Volff, Jean-Nicolas;Genet, Carine;Wincker, Patrick;Jaillon, Olivier;Roest Crollius, Hugues;Guiguen, Yann
通讯作者：
Guiguen, Yann
影响因子：
--
作者：
Anand, A. Alwin Prem;Huber, Carola;Wizenmann, Andrea
通讯作者：
Wizenmann, Andrea
影响因子：
4.6
作者：
Delile, Julien;Rayon, Teresa;Sagner, Andreas
通讯作者：
Sagner, Andreas
DOI：
10.1007/978-1-61779-992-1_24
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Lea, Robert;Bonev, Boyan;Papalopulu, Nancy
通讯作者：
Papalopulu, Nancy