MicroRNA 3' ends shorten during adolescent brain maturation.
MicroRNA 3' ends shorten during adolescent brain maturation.
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DOI：
10.3389/fnmol.2023.1168695
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发表时间：
2023
影响因子：
4.8
通讯作者：
Zakharenko, Stanislav S.
中科院分区：
文献类型：
--
作者：
Thomas, Kristen T.;Vermare, Anais;Egleston, Suzannah O.;Wang, Yong-Dong;Mishra, Ashutosh;Lin, Tong;Peng, Junmin;Zakharenko, Stanislav S.
关键词：
MicroRNA （miRNA）失调在精神疾病中有充分的证据，但在青少年和成年早期大脑成熟过程中，miRNA动力学仍然知之甚少，而症状通常是在这个时候首次出现的。在这里，我们使用RNA测序来检测早期、中期、晚期青少年和成年小鼠皮层和海马中的mirna及其mRNA靶点。此外，我们通过串联质谱标记质谱（TMT-MS）使用定量蛋白质组学来检测来自同一受试者的皮层中的蛋白质动态。我们发现，约25%的miRNAs ‘ 3 ’端随着年龄的增长而缩短，这是由于3 '修剪增加和U尾减少。特别是，miR-338-3p的较短但功能有效的异构体（isomir）在青春期增加了10倍，并且仅在大脑中。与具有稳定3′端的mirna相比，发生3′端缩短的mirna与随着年龄增长而减少的靶标表现出更强的负相关，与随着年龄增长而增加的靶标表现出更强的正相关。在现有的小鼠和人类miRNA-seq数据集中也观察到3 '缩短随着年龄的增长而增加，并且在三个可用数据集中的两个中观察到缩短的mirna与其mRNA靶标之间存在更强的相关性。我们得出结论，年龄相关的miRNA 3 '缩短是出生后大脑成熟的一个保守特征。
MicroRNA (miRNA) dysregulation is well-documented in psychiatric disease, but miRNA dynamics remain poorly understood during adolescent and early adult brain maturation, when symptoms often first appear. Here, we use RNA sequencing to examine miRNAs and their mRNA targets in cortex and hippocampus from early-, mid-, and late-adolescent and adult mice. Furthermore, we use quantitative proteomics by tandem mass tag mass spectrometry (TMT-MS) to examine protein dynamics in cortex from the same subjects. We found that ~25% of miRNAs’ 3′ ends shorten with age due to increased 3′ trimming and decreased U tailing. Particularly, shorter but functionally competent isoforms (isomiRs) of miR-338-3p increase up to 10-fold during adolescence and only in brain. MiRNAs that undergo 3′ shortening exhibit stronger negative correlations with targets that decrease with age and stronger positive correlations with targets that increase with age, than miRNAs with stable 3′ ends. Increased 3′ shortening with age was also observed in available mouse and human miRNA-seq data sets, and stronger correlations between miRNAs that undergo shortening and their mRNA targets were observed in two of the three available data sets. We conclude that age-associated miRNA 3′ shortening is a well-conserved feature of postnatal brain maturation.
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影响因子：
11
作者：
Bavamian, S.;Mellios, N.;Lalonde, J.;Fass, D. M.;Wang, J.;Sheridan, S. D.;Madison, J. M.;Zhou, Fen;Rueckert, E. H.;Barker, D.;Perlis, R. H.;Sur, M.;Haggarty, S. J.
通讯作者：
Haggarty, S. J.
影响因子：
8.8
作者：
Fertuzinhos S;Li M;Kawasawa YI;Ivic V;Franjic D;Singh D;Crair M;Sestan N
通讯作者：
Sestan N
影响因子：
14.9
作者：
Chang, Le;Zhou, Guangyan;Xia, Jianguo
通讯作者：
Xia, Jianguo
影响因子：
6.6
作者：
Beveridge, Natalie J.;Santarelli, Danielle M.;Cairns, Murray J.
通讯作者：
Cairns, Murray J.
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.