Tumor Suppressor MiR-317 and LncRNA Peony Are Expressed from a Polycistronic Non-coding RNA Locus That Regulates Germline Differentiation and Testis Morphology

Overview

Journal bioRxiv

Date 2024 Oct 17

PMID 39416153

Authors

Travis D Carney

Halyna R Shcherbata

Affiliations

Soon will be listed here.

Abstract

This research focuses on investigating the impact of non-coding RNAs on stem cell biology and differentiation processes. We found that plays a role in germline stem cell progeny differentiation. and its neighbor, the lncRNA , originate and are co-expressed from a singular polycistronic non-coding RNA locus. Alternative polyadenylation is implicated in regulation of their differential expression. While the increased expression of the lncRNA results in the disruption of the muscle sheath covering the testis, the absence of leads to the emergence of germline tumors in young flies. The deficiency of increases Notch signaling activity in the somatic cyst cells, which drives germline tumorigenesis. Germline tumors also arise from upregulation of several predicted targets of , among which are regulators of the Notch pathway. This implicates as a novel tumor suppressor that modulates Notch signaling strength.

References

de Cuevas M, Matunis E . The stem cell niche: lessons from the Drosophila testis. Development. 2011; 138(14):2861-9. PMC: 3119301. DOI: 10.1242/dev.056242. View

Fairchild M, Islam F, Tanentzapf G . Identification of genetic networks that act in the somatic cells of the testis to mediate the developmental program of spermatogenesis. PLoS Genet. 2017; 13(9):e1007026. PMC: 5634645. DOI: 10.1371/journal.pgen.1007026. View

Edwards A, Zwarts L, Yamamoto A, Callaerts P, Mackay T . Mutations in many genes affect aggressive behavior in Drosophila melanogaster. BMC Biol. 2009; 7:29. PMC: 2707370. DOI: 10.1186/1741-7007-7-29. View

Pushpavalli S, Sarkar A, Bag I, Hunt C, Ramaiah M, Pandita T . Argonaute-1 functions as a mitotic regulator by controlling Cyclin B during Drosophila early embryogenesis. FASEB J. 2013; 28(2):655-66. PMC: 6191000. DOI: 10.1096/fj.13-231167. View

Joti P, Ghosh-Roy A, Ray K . Dynein light chain 1 functions in somatic cyst cells regulate spermatogonial divisions in Drosophila. Sci Rep. 2012; 1:173. PMC: 3240984. DOI: 10.1038/srep00173. View

Shcherbata H, Ward E, Fischer K, Yu J, Reynolds S, Chen C . Stage-specific differences in the requirements for germline stem cell maintenance in the Drosophila ovary. Cell Stem Cell. 2008; 1(6):698-709. PMC: 2211735. DOI: 10.1016/j.stem.2007.11.007. View

Kerridge S, Thomas-Cavallin M . Appendage morphogenesis in Drosophila: a developmental study of the rotund (rn) gene. Rouxs Arch Dev Biol. 2017; 197(1):19-26. DOI: 10.1007/BF00376037. View

Jensen T, Jacquier A, Libri D . Dealing with pervasive transcription. Mol Cell. 2013; 52(4):473-84. DOI: 10.1016/j.molcel.2013.10.032. View

Cabili M, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A . Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011; 25(18):1915-27. PMC: 3185964. DOI: 10.1101/gad.17446611. View

10.

Brennan K, Tateson R, Lieber T, Couso J, Zecchini V, Arias A . The abruptex mutations of notch disrupt the establishment of proneural clusters in Drosophila. Dev Biol. 1999; 216(1):230-42. DOI: 10.1006/dbio.1999.9501. View

11.

Chen Y, Song S, Weng R, Verma P, Kugler J, Buescher M . Systematic study of Drosophila microRNA functions using a collection of targeted knockout mutations. Dev Cell. 2014; 31(6):784-800. DOI: 10.1016/j.devcel.2014.11.029. View

12.

Ward E, Shcherbata H, Reynolds S, Fischer K, Hatfield S, Ruohola-Baker H . Stem cells signal to the niche through the Notch pathway in the Drosophila ovary. Curr Biol. 2006; 16(23):2352-8. DOI: 10.1016/j.cub.2006.10.022. View

13.

MacDonald C . Tissue-specific mechanisms of alternative polyadenylation: Testis, brain, and beyond (2018 update). Wiley Interdiscip Rev RNA. 2019; 10(4):e1526. PMC: 6617714. DOI: 10.1002/wrna.1526. View

14.

Vied C, Kalderon D . Hedgehog-stimulated stem cells depend on non-canonical activity of the Notch co-activator Mastermind. Development. 2009; 136(13):2177-86. PMC: 2729338. DOI: 10.1242/dev.035329. View

15.

Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U . The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature. 2014; 505(7485):635-40. DOI: 10.1038/nature12943. View

16.

Greenspan L, de Cuevas M, Matunis E . Genetics of gonadal stem cell renewal. Annu Rev Cell Dev Biol. 2015; 31:291-315. PMC: 4659427. DOI: 10.1146/annurev-cellbio-100913-013344. View

17.

Uhlmann S, Mannsperger H, Zhang J, Horvat E, Schmidt C, Kublbeck M . Global microRNA level regulation of EGFR-driven cell-cycle protein network in breast cancer. Mol Syst Biol. 2012; 8:570. PMC: 3293631. DOI: 10.1038/msb.2011.100. View

18.

Young R, Marques A, Tibbit C, Haerty W, Bassett A, Liu J . Identification and properties of 1,119 candidate lincRNA loci in the Drosophila melanogaster genome. Genome Biol Evol. 2012; 4(4):427-42. PMC: 3342871. DOI: 10.1093/gbe/evs020. View

19.

Hart M, Walch-Ruckheim B, Krammes L, Kehl T, Rheinheimer S, Tanzer T . miR-34a as hub of T cell regulation networks. J Immunother Cancer. 2019; 7(1):187. PMC: 6636054. DOI: 10.1186/s40425-019-0670-5. View

20.

Wen K, Yang L, Xiong T, Di C, Ma D, Wu M . Critical roles of long noncoding RNAs in Drosophila spermatogenesis. Genome Res. 2016; 26(9):1233-44. PMC: 5052038. DOI: 10.1101/gr.199547.115. View