Somatic PiRNA and PIWI-mediated Post-transcriptional Gene Regulation in Stem Cells and Disease

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2024 Dec 24

PMID 39717847

Authors

Mahammed Zaid Patel

Yuguan Jiang

Pavan Kumar Kakumani

Affiliations

Soon will be listed here.

Abstract

PIWI-interacting RNAs (piRNAs) are small non-coding RNAs that bind to the PIWI subclass of the Argonaute protein family and are essential for maintaining germline integrity. Initially discovered in , PIWI proteins safeguard piRNAs, forming ribonucleoprotein (RNP) complexes, crucial for regulating gene expression and genome stability, by suppressing transposable elements (TEs). Recent insights revealed that piRNAs and PIWI proteins, known for their roles in germline maintenance, significantly influence mRNA stability, translation and retrotransposon silencing in both stem cells and bodily tissues. In the current review, we explore the multifaceted roles of piRNAs and PIWI proteins in numerous biological contexts, emphasizing their involvement in stem cell maintenance, differentiation, and the development of human diseases. Additionally, we discussed the up-and-coming animal models, beyond the classical fruit fly and earthworm systems, for studying piRNA-PIWIs in self-renewal and cell differentiation. Further, our review offers new insights and discusses the emerging roles of piRNA-dependent and independent functions of PIWI proteins in the soma, especially the mRNA regulation at the post-transcriptional level, governing stem cell characteristics, tumor development, and cardiovascular and neurodegenerative diseases.

References

Jiang H, Hong T, Wang T, Wang X, Cao L, Xu X . Gene expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation. J Cell Physiol. 2018; 234(5):7070-7077. DOI: 10.1002/jcp.27461. View

Rinkevich B, Ballarin L, Martinez P, Somorjai I, Ben-Hamo O, Borisenko I . A pan-metazoan concept for adult stem cells: the wobbling Penrose landscape. Biol Rev Camb Philos Soc. 2021; 97(1):299-325. PMC: 9292022. DOI: 10.1111/brv.12801. View

Gao Q, Wang L, Wang S, Huang B, Jing Y, Su J . Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation. Front Cell Dev Biol. 2022; 9:787118. PMC: 8762234. DOI: 10.3389/fcell.2021.787118. View

Liu J, Chen M, Ma L, Dang X, Du G . piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification. Aging (Albany NY). 2021; 13(19):23361-23375. PMC: 8544320. DOI: 10.18632/aging.203630. View

Reitzel A, Pang K, Martindale M . Developmental expression of "germline"- and "sex determination"-related genes in the ctenophore Mnemiopsis leidyi. Evodevo. 2016; 7:17. PMC: 4971632. DOI: 10.1186/s13227-016-0051-9. View

Sturm A, Saskoi E, Hotzi B, Tarnoci A, Barna J, Bodnar F . Downregulation of transposable elements extends lifespan in Caenorhabditis elegans. Nat Commun. 2023; 14(1):5278. PMC: 10465613. DOI: 10.1038/s41467-023-40957-9. View

Balaratnam S, West N, Basu S . A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy chain 1 mRNA in human somatic cells. Nucleic Acids Res. 2018; 46(20):10635-10648. PMC: 6237762. DOI: 10.1093/nar/gky728. View

Sohn E, Oh S . P-Element-Induced Wimpy Testis Proteins and P-Element-Induced Wimpy Testis-Interacting RNAs Expression in Ovarian Cancer Stem Cells. Genet Test Mol Biomarkers. 2023; 27(2):56-64. DOI: 10.1089/gtmb.2022.0113. View

Kim I, Duncan E, Ross E, Gorbovytska V, Nowotarski S, Elliott S . Planarians recruit piRNAs for mRNA turnover in adult stem cells. Genes Dev. 2019; 33(21-22):1575-1590. PMC: 6824462. DOI: 10.1101/gad.322776.118. View

10.

Liu Y, Dou M, Song X, Dong Y, Liu S, Liu H . The emerging role of the piRNA/piwi complex in cancer. Mol Cancer. 2019; 18(1):123. PMC: 6688334. DOI: 10.1186/s12943-019-1052-9. View

11.

Ayyaz A, Jasper H . Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster. Front Cell Infect Microbiol. 2014; 3:98. PMC: 3863754. DOI: 10.3389/fcimb.2013.00098. View

12.

Dattani A, Sridhar D, Aboobaker A . Planarian flatworms as a new model system for understanding the epigenetic regulation of stem cell pluripotency and differentiation. Semin Cell Dev Biol. 2018; 87:79-94. DOI: 10.1016/j.semcdb.2018.04.007. View

13.

Ramat A, Simonelig M . Functions of PIWI Proteins in Gene Regulation: New Arrows Added to the piRNA Quiver. Trends Genet. 2020; 37(2):188-200. DOI: 10.1016/j.tig.2020.08.011. View

14.

Ho S, Theurkauf W, Rice N . piRNA-Guided Transposon Silencing and Response to Stress in Germline. Viruses. 2024; 16(5). PMC: 11125864. DOI: 10.3390/v16050714. View

15.

Ninova M, Chen Y, Godneeva B, Rogers A, Luo Y, Fejes Toth K . Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing. Mol Cell. 2020; 77(3):556-570.e6. PMC: 7007863. DOI: 10.1016/j.molcel.2019.11.012. View

16.

Dayeh D, Kruithoff B, Nakanishi K . Structural and functional analyses reveal the contributions of the C- and N-lobes of Argonaute protein to selectivity of RNA target cleavage. J Biol Chem. 2018; 293(17):6308-6325. PMC: 5925815. DOI: 10.1074/jbc.RA117.001051. View

17.

Wu Y, Wang J, Zhang P, Yuan L, Ju L, Wang H . PIWIL1 interacting RNA piR-017724 inhibits proliferation, invasion, and migration, and inhibits the development of HCC by silencing PLIN3. Front Oncol. 2023; 13:1203821. PMC: 10369847. DOI: 10.3389/fonc.2023.1203821. View

18.

Ninova M, Godneeva B, Chen Y, Luo Y, Prakash S, Jankovics F . The SUMO Ligase Su(var)2-10 Controls Hetero- and Euchromatic Gene Expression via Establishing H3K9 Trimethylation and Negative Feedback Regulation. Mol Cell. 2020; 77(3):571-585.e4. PMC: 7007874. DOI: 10.1016/j.molcel.2019.09.033. View

19.

Zhu Y, Fan C, Zhao B . Differential expression of piRNAs in reprogrammed pluripotent stem cells from mouse embryonic fibroblasts. IUBMB Life. 2019; 71(12):1906-1915. DOI: 10.1002/iub.2128. View

20.

Genzor P, Cordts S, Bokil N, Haase A . Aberrant expression of select piRNA-pathway genes does not reactivate piRNA silencing in cancer cells. Proc Natl Acad Sci U S A. 2019; 116(23):11111-11112. PMC: 6561285. DOI: 10.1073/pnas.1904498116. View