Mathias S. Renaud

Bio: Mathias S. Renaud is an academic researcher from University of Toronto. The author has contributed to research in topics: Gene & Argonaute. The author has an hindex of 3, co-authored 3 publications receiving 10 citations.

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

Abstract: The Caenorhabditis elegans genome encodes nineteen functional Argonaute proteins that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one Argonaute is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG into the long (CSR-1a) and short (CSR-1b) isoforms, we found that CSR-1a is expressed during spermatogenesis and in several somatic tissues, including the intestine. CSR-1b is expressed constitutively in the germline. small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. Phenotypic analyses reveal that the essential functions of csr-1 described in the literature coincide with CSR-1b, while CSR-1a plays tissue specific functions. During spermatogenesis, CSR-1a integrates into an sRNA regulatory network including ALG-3, ALG-4 and WAGO-10 that is necessary for fertility at 25°C. In the intestine, CSR-1a silences immunity and pathogen-responsive genes, and its loss results in improved survival from the pathogen Pseudomonas aeruginosa. Our findings functionally distinguish the CSR-1 isoforms and highlight the importance of studying each AGO isoform independently.

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility through distinct small RNA classes

Abstract: The C. elegans genome encodes nineteen functional Argonaute proteins that utilize 22G-RNAs, 26G-RNAs, miRNAs, or piRNAs to regulate their target transcripts. Only one of these proteins is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied in various developmental and functional contexts, nearly all studies investigating CSR-1 have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG epitopes into the long (CSR-1a) and short (CSR-1b) isoforms of CSR-1, we identified differential expression patterns for the two isoforms. CSR-1a is expressed specifically during spermatogenesis and in select somatic tissues, including the intestine. In contrast, CSR-1b, is expressed constitutively in the germline. Essential functions of csr-1 described in the literature coincide with CSR-1b. In contrast, CSR-1a plays tissue specific functions during spermatogenesis, where it integrates into a spermatogenesis sRNA regulatory network including ALG-3, ALG-4, and WAGO-10 that is necessary for male fertility. CSR-1a is also required in the intestine for the silencing of repetitive transgenes. Sequencing of small RNAs associated with each CSR-1 isoform reveals that CSR-1a engages with 22G- and 26G-RNAs, while CSR-1b interacts with only 22G-RNAs to regulate distinct groups of germline genes and regulate both sperm and oocyte-mediated fertility.

Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility

Abstract: The C. elegans genome encodes nineteen functional Argonaute proteins that utilize 22G-RNAs, 26G-RNAs, miRNAs, or piRNAs to regulate their target transcripts. Only one Argonaute is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG into the long (CSR-1a) and short (CSR-1b) isoforms, we found that CSR-1a is expressed during spermatogenesis and in several somatic tissues, including the intestine. CSR-1b is expressed constitutively in the germline. small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. Phenotypic analyses reveal that the essential functions of csr-1 described in the literature coincide with CSR-1b, while CSR-1a plays tissue specific functions. During spermatogenesis, CSR-1a integrates into an sRNA regulatory network including ALG-3, ALG-4, and WAGO-10 that is necessary for fertility at 25°C. In the intestine, CSR-1a silences immunity and pathogen-responsive genes, and its loss results in improved survival from the pathogen Pseudomonas aeruginosa. Our findings functionally distinguish the CSR-1 isoforms and highlight the importance of studying each AGO isoform independently.

Small RNAs and chromatin in the multigenerational epigenetic landscape of Caenorhabditis elegans.

Abstract: For decades, it was thought that the only heritable information transmitted from one individual to another was that encoded in the DNA sequence. However, it has become increasingly clear that this is not the case and that the transmission of molecules from within the cytoplasm of the gamete also plays a significant role in heritability. The roundworm, Caenorhabditis elegans, has emerged as one of the leading model organisms in which to study the mechanisms of transgenerational epigenetic inheritance (TEI). Collaborative efforts over the past few years have revealed that RNA molecules play a critical role in transmitting transgenerational responses, but precisely how they do so is as yet uncertain. In addition, the role of histone modifications in epigenetic inheritance is increasingly apparent, and RNA and histones interact in a way that we do not yet fully understand. Furthermore, both exogenous and endogenous RNA molecules, as well as other environmental triggers, are able to induce heritable epigenetic changes that affect transcription across the genome. In most cases, these epigenetic changes last only for a handful of generations, but occasionally can be maintained much longer: perhaps indefinitely. In this review, we discuss the current understanding of the role of RNA and histones in TEI, as well as making clear the gaps in our knowledge. We also speculate on the evolutionary implications of epigenetic inheritance, particularly in the context of a short-lived, clonally propagating species. This article is part of the theme issue 'How does epigenetics influence the course of evolution?'

Germ granules and gene regulation in the Caenorhabditis elegans germline.

Abstract: The transparency of Caenorhabditis elegans provides a unique window to observe and study the function of germ granules. Germ granules are specialized ribonucleoprotein (RNP) assemblies specific to the germline cytoplasm, and they are largely conserved across Metazoa. Within the germline cytoplasm, they are positioned to regulate mRNA abundance, translation, small RNA production, and cytoplasmic inheritance to help specify and maintain germline identity across generations. Here we provide an overview of germ granules and focus on the significance of more recent observations that describe how they further demix into sub-granules, each with unique compositions and functions.