miRNAs cooperate in apoptosis regulation during C. elegans development
Ryan Sherrard 1,3, Sebastian Luehr 1,3, Heinke Holzkamp 1, Katherine McJunkin 2, Nadin Memar 1 and Barbara Conradt 1
- Author Affiliations
1Center for Integrated Protein Science Munich – CIPSM, Department Biology II, Ludwig-Maximilians-University Munich, Planegg-Martinsried 82152, Germany;
2Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01606, USA
Corresponding authors: conradt@bio.lmu.de, memar@bio.lmu.de
↵3 These authors contributed equally to this work.
Source/Fonte: Google Images
Abstract
Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of egl-1 is dependent on binding sites for miR-35 and miR-58 family miRNAs within the egl-1 3′ untranslated region (UTR), which affect both mRNA copy number and translation. Furthermore, using single-molecule RNA fluorescent in situ hybridization (smRNA FISH), we show that egl-1 is transcribed in the mother of a cell programmed to die and that miR-35 and miR-58 family miRNAs prevent this mother from dying by keeping the copy number of egl-1 mRNA below a critical threshold. Finally, miR-35 and miR-58 family miRNAs can also dampen the transcriptional boost of egl-1 that occurs specifically in a daughter cell that is programmed to die. We propose that miRNAs compensate for lineage-specific differences in egl-1 transcriptional activation, thus ensuring that EGL-1 activity reaches the threshold necessary to trigger death only in daughter cells that are programmed to die.
Keywords miRNA programmed cell death BH3-only development embryo C. elegans
Footnotes
Supplemental material is available for this article.
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.288555.116.
Freely available online through the Genes & Development Open Access option.
Received August 4, 2016 Accepted January 11, 2017.
© 2017 Sherrard et al.; Published by Cold Spring Harbor Laboratory Press
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
FREE PDF GRATIS: Genes and Development Sup. Info.
+++++
NOTA DESTE BLOGGER:
A morte programada das células, conhecida como apoptose, é um processo fundamental e altamente regulado que ocorre em todos os organismos chamados de superiores. É um processo essencial para o desenvolvimento embrionário normal, durante o qual células supérfluas devem ser descartadas, mas de forma ordenada.
Mero acaso, fortuita necessidade ou 100% design inteligente?
Mero acaso, fortuita necessidade ou 100% design inteligente?
