Publications by authors named "Florian Constanty"

3 Publications

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lncRNAs in development and differentiation: from sequence motifs to functional characterization.

Development 2021 Jan 13;148(1). Epub 2021 Jan 13.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris 75005, France

The number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners.
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http://dx.doi.org/10.1242/dev.182741DOI Listing
January 2021

Strategies for genetic inactivation of long noncoding RNAs in zebrafish.

RNA 2019 08 1;25(8):897-904. Epub 2019 May 1.

Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, 75005 Paris, France.

The number of annotated long noncoding RNAs (lncRNAs) continues to grow; however, their functional characterization in model organisms has been hampered by the lack of reliable genetic inactivation strategies. While partial or full deletions of lncRNA loci disrupt lncRNA expression, they do not permit the formal association of a phenotype with the encoded transcript. Here, we examined several alternative strategies for generating lncRNA null alleles in zebrafish and found that they often resulted in unpredicted changes to lncRNA expression. Removal of the transcription start sites (TSSs) of lncRNA genes resulted in hypomorphic mutants, due to the usage of either constitutive or tissue-specific alternative TSSs. Deletions of short, highly conserved lncRNA regions can also lead to overexpression of truncated transcripts. In contrast, knock-in of a polyadenylation signal enabled complete inactivation of , the most abundant vertebrate lncRNA. In summary, lncRNA null alleles require extensive in vivo validation, and we propose insertion of transcription termination sequences as the most reliable approach to generate lncRNA-deficient zebrafish.
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http://dx.doi.org/10.1261/rna.069484.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6633201PMC
August 2019