Publications
Sun, Y.H., and Li, X.Z. (2021) The birth of piRNAs: How mammalian piRNAs are produced, originated, and evolved. In press.
Sun, Y.H., Wang, R.H., Du, K., Zhu, J., Zheng, J., Xie, L.H., Pereira A., Zhang, C., Ricci, E.P., and Li, X.Z. (2021) Coupled protein synthesis and ribosome-guided piRNA processing on mRNAs. Nature Communications. 12,5970
Highlighted in BioArt : https://mp.weixin.qq.com/s/DLAeDHzS0It4Nqa6K5af_w
Gu, H., Yu, Y.H., Li, X.Z. (2021) Novel rRNA-depletion methods for total RNA sequencing and ribosome profiling developed for avian species. Poultry Science. 100:101321
Sun, Y.H., Wang, A., Song, C., Shankar G., Srivastava, R.K., Au, K.F., Li X.Z. (2021) Single-molecule long-read sequencing reveals a conserved intact long RNA profile in sperm. Nature Communications, 12, 1361
Highlighted in : Wang, Z., Chen, S., & Yan, W. (2021). Both murine and human sperm contain intact large RNAs. Biology of reproduction, ioab055. Advance online publication. https://doi.org/10.1093/biolre/ioab055
Highlighted in BioArt : https://mp.weixin.qq.com/s/4uSjSdkvrnRfBOHqZdU2tw
While dogma states that sperm is a bottleneck for epigenetic information transfer, paternal diet or experiences can impact offspring phenotypes. This phenomenon known as epigenetic inheritance raises three fundamental questions: 1) How does soma-to-germline communication occur? 2) How is information transmitted to the subsequent generation? 3) How is the initial trigger maintained and amplified leading to a long-term impact? Recent studies have shown that sperm RNA carries information to the next generation. Because sperm is translationally quiescent, it was believed that sperm RNAs are globally fragmented with only small RNAs left for transgenerational function. Because short-read sequencing cannot distinguish intact RNAs from fragmented RNAs, the question of whether intact mRNAs exist in sperm remained unsolved. Here, using single-molecule long-read sequencing and building a bioinformatic pipeline, we identified thousands of sperm intact mRNA species (spiRNA) in mice and humans. The spiRNA profile, including functional enrichment for protein synthesis, is evolutionarily conserved between rodents and primates, suggesting the function of spiRNAs in promoting zygotic protein synthesis and the presence of an active selection mechanism specifying spiRNA profiles. This study opens new avenues to understanding sperm RNA function and how environments modulate the spiRNA profile.
Abe, H., Meduri, R., Li, Z., Andreassen P.R., Li, X.Z., Namekawa S.H. (2020) RNF8 is not required for histone-to-protamine exchange in spermiogenesis. bioRxiv.2020.12.05.413005
Avidor-Reiss, T., Zhang, Z., Li, X.Z. (2020) Sperm differentiation and spermatozoa function: mechanisms, diagnostics, and treatment. Frontiers in Cell and Developmental Biology; 8:219
Sun, Y.H., Zhu, J., Xie, L.H., Li, Z., Meduri, R., Zhu, X., Song, C., Ricci, E.P., Weng, Z., and Li, X.Z. Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors. Nature Cell Biology, 2020: 1-13
Highlighted in: Mao, Yuanhui, and Shu-Bing Qian. Ribosome-guided piRNA production. Nature Cell Biology, 2020: 1-2
Highlighted in BioArt : https://mp.weixin.qq.com/s/pWtvLsPqmlxlDG9MNAV4jg
piRNAs, essential for fertility, are the most heterogeneous RNAs with > 1 million unique sequences in each human individual and have a biogenesis distinct from any other RNA. During my postdoc training, I defined the precise transcript structure of piRNA precursors in mammals as long, continuous single strand RNAs from intergenic regions, opening the study of their post-transcriptional processing. These precursors are fragmented in a stepwise manner from the 5´ to 3´ direction, generating tens and thousands of pieces that become piRNAs. This fragmentation process determines piRNA 5´ ends and subsequently determines the target sequences piRNAs can recognize. Beyond this, it was unclear how piRNA 5´ ends are specified and how piRNA biogenesis is sustained on long precursors. While piRNA precursors are annotated as non-coding RNAs, we found that ribosomes translate short upstream open reading frames then spread throughout transcripts. Bound ribosomes guide the processing of precursor RNAs such that the regions protected by ribosomes determine the location of mature piRNAs. This finding challenges the current dogma that ribosomes cannot translocate processively on non-coding regions with frequent stop codons, indicating special translational control mechanisms in germ cells and revealing a new function of ribosomes in guiding piRNA formation.
Li, X.Z. What can piRNA research learn from chickens, and vice versa? Canadian Journal of Animal Science, 2019, ja
Sun, Y.H., Jiang F., and Li, X.Z. Disruption of Tdrd5 decouples the stepwise processing of long precursor transcripts during pachytene piRNA biogenesis. Biology of Reproduction, 2018. ioy110
Sun, Y.H., Xie, L.H., Zhuo, X., Chen, Q., Ghoneim, D., Zhang, B., Jagne, J., Yang, C., and Li, X.Z. Domestic chickens activate a piRNA defense against avian leukosis virus. ELife, 2017. Apr 6;6. PMID: 28384097
Highlighted in URMC Research News, ScienceDaily and Phys.org.
Our work addressed a fundamental question: when retroviruses endogenize into animal genomes, how do hosts recognize self vs non-self sequences? While piRNAs are known to be the major RNA-based defense mechanism protecting germline genomes from transposable element (TE) activation, it remains unclear how hosts acquire new piRNA sequences. However, avian leukosis virus, which invaded the chicken genome recently and remains infectious, provided us a unique opportunity to address this question. Comparing domestic chickens with wild chickens, we found that domestic chickens hijacks a preexisting provirus into a new piRNA-producing locus, reminiscent of the CRISPR system in bacteria. This piRNA-producing provirus has long been known to have an antiviral function during chicken breeding, a phenomenon known as viral interference. Thus, our work not only discovers an antiviral function for piRNAs, but also explains viral interference. This hijacking of newly-invaded viral sequences into piRNAs is found in mammals as well, representing a common host strategy to generate new piRNAs as self-defense weapons.