Pollini Daniele, Loffredo Rosa, Maniscalco Federica, Cardano Marina, Micaelli Mariachiara, Bonomo Isabelle, Licata Nausicaa Valentina, Peroni Daniele, Tomaszewska Weronika, Rossi Annalisa, Crippa Valeria, Dassi Erik, Viero Gabriella, Quattrone Alessandro, Poletti Angelo, Conti Luciano, Provenzani Alessandro
Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
Institute of Biophysics, CNR, Trento, Italy.
iScience. 2021 Feb 16;24(3):102197. doi: 10.1016/j.isci.2021.102197. eCollection 2021 Mar 19.
Matrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays pleiotropic roles in gene expression regulation by directly stabilizing target RNAs and supporting the activity of transcription factors by modulating chromatin architecture. MATR3 is involved in the differentiation of neural cells, and, here, we elucidate its critical functions in regulating pluripotent circuits in human induced pluripotent stem cells (hiPSCs). MATR3 downregulation affects hiPSCs' differentiation potential by altering key pluripotency regulators' expression levels, including OCT4, NANOG, and LIN28A by pleiotropic mechanisms. MATR3 binds to the and promoters favoring their expression. YTHDF1, in turn, binds the m6A-modified OCT4 mRNA. Furthermore, MATR3 is recruited on ribosomes and controls pluripotency regulating the translation of specific transcripts, including NANOG and LIN28A, by direct binding and favoring their stabilization. These results show that MATR3 orchestrates the pluripotency circuitry by regulating the transcription, translational efficiency, and epitranscriptome of specific transcripts.
Matrin3（MATR3）是一种核RNA/DNA结合蛋白，通过直接稳定靶RNA并通过调节染色质结构来支持转录因子的活性，在基因表达调控中发挥多效性作用。MATR3参与神经细胞的分化，在此，我们阐明其在调节人诱导多能干细胞（hiPSC）多能性回路中的关键功能。MATR3下调通过多效性机制改变关键多能性调节因子的表达水平，包括OCT4、NANOG和LIN28A，从而影响hiPSC的分化潜能。MATR3与 和 启动子结合，促进它们的表达。反过来，YTHDF1与m6A修饰的OCT4 mRNA结合。此外，MATR3被招募到核糖体上，并通过直接结合和促进特定转录本（包括NANOG和LIN28A）的稳定来控制多能性，调节其翻译。这些结果表明，MATR3通过调节特定转录本的转录、翻译效率和表观转录组来协调多能性回路。
