Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference

Javier J Castro Alvarez; Maxime Revel; Judit Carrasco; Fabienne Cléard; Daniel Pauli; Valérie Hilgers; François Karch; Robert K Maeda

doi:10.1371/journal.pgen.1009843

Repression of the Hox gene abd-A by ELAV-mediated Transcriptional Interference

PLoS Genet. 2021 Nov 15;17(11):e1009843. doi: 10.1371/journal.pgen.1009843. eCollection 2021 Nov.

Authors

Javier J Castro Alvarez¹, Maxime Revel¹, Judit Carrasco^{2

3}, Fabienne Cléard¹, Daniel Pauli¹, Valérie Hilgers², François Karch¹, Robert K Maeda¹

Affiliations

¹ Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland.
² Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
³ Faculty of Biology, Albert Ludwig University, Freiburg, Germany.

Abstract

Intergenic transcription is a common feature of eukaryotic genomes and performs important and diverse cellular functions. Here, we investigate the iab-8 ncRNA from the Drosophila Bithorax Complex and show that this RNA is able to repress the transcription of genes located at its 3' end by a sequence-independent, transcriptional interference mechanism. Although this RNA is expressed in the early epidermis and CNS, we find that its repressive activity is limited to the CNS, where, in wild-type embryos, it acts on the Hox gene, abd-A, located immediately downstream of it. The CNS specificity is achieved through a 3' extension of the transcript, mediated by the neuronal-specific, RNA-binding protein, ELAV. Loss of ELAV activity eliminates the 3' extension and results in the ectopic activation of abd-A. Thus, a tissue-specific change in the length of a ncRNA is used to generate a precise pattern of gene expression in a higher eukaryote.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Clustered Regularly Interspaced Short Palindromic Repeats
Drosophila Proteins / genetics*
Drosophila melanogaster / embryology
Drosophila melanogaster / genetics*
ELAV Proteins / genetics*
Genes, Homeobox*
Genes, Reporter
MicroRNAs / genetics
Nuclear Proteins / genetics*
RNA, Long Noncoding / genetics
Sequence Deletion
Transcription Factors / genetics*
Transcription, Genetic*

Substances

Drosophila Proteins
ELAV Proteins
ELAV protein, Drosophila
MicroRNAs
Nuclear Proteins
RNA, Long Noncoding
Transcription Factors
abd-A protein, Drosophila

Grants and funding

This work was supported by the Canton of Geneva (R.K.M and F.K.), the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 31003A_149634 (to F.K. and R.K.M.) and grant 310030_192621 (to R.K.M)., the Claraz Foundation (to F.K., R.K.M. and D.P.), the Max Planck Society (https://www.mpg.de), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (https://www.dfg.de) Project-ID 403222702 - SFB 1381 (to V.H.) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program ((https://erc.europa.eu) grant agreement no. ERC-2018-STG-803258 (to V.H.). Salaries for J.J.C.A., R.K.M, D.P. and F.K. were paid by the Canton of Geneva. The salaries of F.C. and J.J.C.A. were paid by the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 31003A_149634 (to F.K. and R.K.M.). The salary of M.R. was paid by the Swiss National Fund for Research (http://www.snf.ch/Seiten/VariationRoot.aspx) grant 310030_192621 (to R.K.M). The salary of J.C. was paid by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program ((https://erc.europa.eu) grant agreement no. ERC-2018-STG-803258 (to V.H.). And the salary of V.H was paid by the Max Planck Society (https://www.mpg.de). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.