A Genetic Screen Identifies and As Pro-apoptotic Genes and Potential Activators of Expression

Overview

Journal MicroPubl Biol

Specialty Biology

Date 2024 Mar 4

PMID 38434221

Authors

Yanwen Jiang

Barbara Conradt

Affiliations

Soon will be listed here.

Abstract

During development, 1090 somatic cells are generated of which 131 reproducibly die, many through apoptosis. The BH3-only gene is the key activator of apoptosis in somatic tissues, and it is predominantly expressed in 'cell death' lineages i.e. lineages in which apoptotic cell death occurs. expression is regulated at the transcriptional and post-transcriptional level. For example, we previously showed that the miR-35 and miR-58 families of miRNAs repress expression in mothers of 'unwanted' cells by binding to the 3' UTR of mRNA, thereby increasing mRNA turnover. In a screen for RNA-binding proteins with a role in the post-transcriptional control of expression, we identified EIF-3.H (ortholog of human eIF3H) and HRPR-1 (ortholog human hnRNP R/Q) as potential activators of expression. In addition, we demonstrate that the knockdown of the or gene by RNA-mediated interference (RNAi) results in the inappropriate survival of unwanted cells during development. Our study provides novel insight into how expression is controlled to cause the reproducible pattern of cell death observed during development.

References

Sulston J, Horvitz H . Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol. 1977; 56(1):110-56. DOI: 10.1016/0012-1606(77)90158-0. View

Matia-Gonzalez A, Laing E, Gerber A . Conserved mRNA-binding proteomes in eukaryotic organisms. Nat Struct Mol Biol. 2015; 22(12):1027-33. PMC: 5759928. DOI: 10.1038/nsmb.3128. View

Conradt B, Wu Y, Xue D . Programmed Cell Death During Caenorhabditis elegans Development. Genetics. 2016; 203(4):1533-62. PMC: 4981262. DOI: 10.1534/genetics.115.186247. View

Sulston J, Schierenberg E, White J, Thomson J . The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol. 1983; 100(1):64-119. DOI: 10.1016/0012-1606(83)90201-4. View

Choudhuri A, Maitra U, Evans T . Translation initiation factor eIF3h targets specific transcripts to polysomes during embryogenesis. Proc Natl Acad Sci U S A. 2013; 110(24):9818-23. PMC: 3683746. DOI: 10.1073/pnas.1302934110. View

Shaham S, Reddien P, Davies B, Horvitz H . Mutational analysis of the Caenorhabditis elegans cell-death gene ced-3. Genetics. 1999; 153(4):1655-71. PMC: 1460877. DOI: 10.1093/genetics/153.4.1655. View

Ariz M, Mainpal R, Subramaniam K . C. elegans RNA-binding proteins PUF-8 and MEX-3 function redundantly to promote germline stem cell mitosis. Dev Biol. 2008; 326(2):295-304. PMC: 2680957. DOI: 10.1016/j.ydbio.2008.11.024. View

Chen F, Hersh B, Conradt B, Zhou Z, Riemer D, Gruenbaum Y . Translocation of C. elegans CED-4 to nuclear membranes during programmed cell death. Science. 2000; 287(5457):1485-9. DOI: 10.1126/science.287.5457.1485. View

Chakraborty S, Lambie E, Bindu S, Mikeladze-Dvali T, Conradt B . Engulfment pathways promote programmed cell death by enhancing the unequal segregation of apoptotic potential. Nat Commun. 2015; 6:10126. PMC: 4682117. DOI: 10.1038/ncomms10126. View

10.

Maduro M, Pilgrim D . Identification and cloning of unc-119, a gene expressed in the Caenorhabditis elegans nervous system. Genetics. 1995; 141(3):977-88. PMC: 1206859. DOI: 10.1093/genetics/141.3.977. View

11.

Rossoll W, Jablonka S, Andreassi C, Kroning A, Karle K, Monani U . Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol. 2003; 163(4):801-12. PMC: 2173668. DOI: 10.1083/jcb.200304128. View

12.

Audhya A, Hyndman F, McLeod I, Maddox A, Yates 3rd J, Desai A . A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans. J Cell Biol. 2005; 171(2):267-79. PMC: 2171198. DOI: 10.1083/jcb.200506124. View

13.

Kamath R, Ahringer J . Genome-wide RNAi screening in Caenorhabditis elegans. Methods. 2003; 30(4):313-21. DOI: 10.1016/s1046-2023(03)00050-1. View

14.

Eckmann C, Kraemer B, Wickens M, Kimble J . GLD-3, a bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Dev Cell. 2002; 3(5):697-710. DOI: 10.1016/s1534-5807(02)00322-2. View

15.

Yan B, Memar N, Gallinger J, Conradt B . Coordination of cell proliferation and cell fate determination by CES-1 snail. PLoS Genet. 2013; 9(10):e1003884. PMC: 3814331. DOI: 10.1371/journal.pgen.1003884. View

16.

Lee A, Kranzusch P, Cate J . eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature. 2015; 522(7554):111-4. PMC: 4603833. DOI: 10.1038/nature14267. View

17.

Tamburino A, Ryder S, Walhout A . A compendium of Caenorhabditis elegans RNA binding proteins predicts extensive regulation at multiple levels. G3 (Bethesda). 2013; 3(2):297-304. PMC: 3564989. DOI: 10.1534/g3.112.004390. View

18.

Frokjaer-Jensen C, Davis M, Ailion M, Jorgensen E . Improved Mos1-mediated transgenesis in C. elegans. Nat Methods. 2012; 9(2):117-8. PMC: 3725292. DOI: 10.1038/nmeth.1865. View

19.

Schmitz C, Kinge P, Hutter H . Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc Natl Acad Sci U S A. 2007; 104(3):834-9. PMC: 1783400. DOI: 10.1073/pnas.0510527104. View

20.

Maurer C, Chiorazzi M, Shaham S . Timing of the onset of a developmental cell death is controlled by transcriptional induction of the C. elegans ced-3 caspase-encoding gene. Development. 2007; 134(7):1357-68. DOI: 10.1242/dev.02818. View