The genome integrity of germ cell is of fundamental importance for maintaining individuals and species. The predominant biological factor that causes genome mutations is mobile genetic elements (such as transposon and retrotransposon). Recently, a new class of 26-32 nt long small RNAs termed as PIWI-interacting RNAs (piRNAs) was discovered in the germ cells of animals, revealing a distinct small RNA pathway that controls the activity of mobile genetic elements. A new study by researchers from Chinese Academy of Sciences showed that piRNA triggers the degredation of its binding protein and itself at a specific developmental stage, shedding new light on the metabolism of the PIWI/piRNA machinery.
Researchers led by Prof. LIU Mofang and Prof. WANG Enduo from Shanghai Institute of Biochemistry and Cell Biology, CAS, study the regulation of PIWI/piRNA metabolism in mouse spermatids. They found that murine PIWI (MIWI) is degraded through the APC/C-26S proteasome pathway. Intriguingly, piRNAs play an indispensable role in this process by enhancing MIWI interaction with an APC/C substrate-binding subunit. Furthermore, they found that piRNA-induced MIWI destruction occurs in late spermatids, which in turn leads to piRNA elimination, suggesting a feed-forward mechanism for coordinated removal of the MIWI/piRNA machinery at a specific developmental stage. Importantly, they showed that stabilization of MIWI in late spermatids led to a blockage of subsequent sperm maturation. Taken together, this study uncovers a mechanism for the developmental regulation of MIWI/piRNA metabolism and suggests the biological importance of such regulation in germ cell development.
This work entitled “piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis” was published in Developmental Cell on January 14th, 2013. This work was funded by grants from Chinese Academy of Sciences, Ministry of Science and Technology, National Natural Science Foundation of China, and Science and Technology Commission of Shanghai Municipality.
AUTHOR CONTACT:
LIU Mofang
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Phone: 86-21-54921146;
E-mail: mfliu@sibcb.ac.cn
A model for coordinated elimination of MIWI and piRNAs in late stages of spermatogenesis. (Image provided by Dr. LIU Mofang)
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