Regulation of L-threonine dehydrogenase in somatic cell reprogramming.
Increasing evidence suggests that metabolic remodeling plays an important role in the regulation of somatic cell reprogramming. Threonine catabolism mediated by L-threonine dehydrogenase (TDH) has been recognized as a specific metabolic trait of mouse embryonic stem cells. However, it remains unknown whether TDH-mediated threonine catabolism could regulate reprogramming. Here, we report TDH as a novel regulator of somatic cell reprogramming. Knockdown of TDH inhibits, whereas induction of TDH enhances reprogramming efficiency. Moreover, microRNA-9 post-transcriptionally regulates the expression of TDH and thereby inhibits reprogramming efficiency. Furthermore, protein arginine methyltransferase (PRMT5) interacts with TDH and mediates its post-translational arginine methylation. PRMT5 appears to regulate TDH enzyme activity through both methyltransferase-dependent and -independent mechanisms. Functionally, TDH-facilitated reprogramming efficiency is further enhanced by PRMT5. These results suggest that TDH-mediated threonine catabolism controls somatic cell reprogramming and indicate the importance of post-transcriptional and post-translational regulation of TDH.
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Chuanchun
C
Han
Hao
H
Gu
Jiaxu
J
Wang
Weiguang
W
Lu
Yide
Y
Mei
Mian
M
Wu
D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D065150:Cellular Reprogramming / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008745:Methylation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D011496:Protein Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases; D034622:RNA Interference; D013234:Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D013912:Threonine / Q000378:metabolism*
C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D013912:Threonine; D001120:Arginine; D000429:Alcohol Oxidoreductases; C023159:L-threonine 3-dehydrogenase; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases