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, 3, e28234

Nematode Endogenous Small RNA Pathways


Nematode Endogenous Small RNA Pathways

Suzanne W Hoogstrate et al. Worm.


The discovery of small RNA silencing pathways has greatly extended our knowledge of gene regulation. Small RNAs have been presumed to play a role in every field of biology because they affect many biological processes via regulation of gene expression and chromatin remodeling. Most well-known examples of affected processes are development, fertility, and maintenance of genome stability. Here we review the role of the three main endogenous small RNA silencing pathways in Caenorhabditis elegans: microRNAs, endogenous small interfering RNAs, and PIWI-interacting RNAs. After providing an entry-level overview on how these pathways function, we discuss research on other nematode species providing insight into the evolution of these small RNA pathways. In understanding the differences between the endogenous small RNA pathways and their evolution, a more comprehensive picture is formed of the functions and effects of small RNAs.

Keywords: Argonaute; C. elegans; RNA interference; RNA silencing; endo-siRNA; miRNA; nematode; piRNA; small RNA.


Figure 1. Phylogeny of sequenced nematodes. Phylogenetic relationship of nematodes that have (part of) their DNA sequences published or are being sequenced (as indicated on The clades are shown according to Van Megen et al. in Arabic numbers and to Blaxter et al. in Roman numbers., In both studies, the phylogenetic relationships were determined by the DNA sequences of the small ribosomal subunits, with 1215 and 53 sequences, respectively. An asterisk indicates that this species has been studied for (some aspects of) the small RNA response.
Figure 2. Small RNAs and developmental dynamics. Panel A shows an example of the size distribution of small RNAs in adult hermaphrodites, adapted from reference . These can be divided over several classes of small RNAs, which are shown in panel B. In panel B, it can be seen that the relative amounts of small RNAs change throughout development and are different between sexes, adapted from reference . This is illustrated in more detail in panel C, where the expression of three different microRNAs is shown throughout the hermaphroditic development, adapted from reference .
Figure 3. Small RNA pathways in C. elegans. Overview of the discussed endogenous small RNA pathways in C. elegans. The dashed line between nucleus and cytoplasm in the piRNA pathway means that it is not clear when the piRNAs leave the nucleus. For the miRNAs and endo-siRNAs, it is known exactly, indicated by a solid line.
Figure 4. Identified Argonaute orthologs in nematodes. Phylogenetic tree of nematodes researched for Argonaute orthologs and the three groups of Argonautes (Argonaute-like, PIWI, and Worm-specific)., The three major types of Argonaute proteins are sub-divided into eight homologous groups. The AGO-A group contains the C. elegans proteins ALG-3 and ALG-4 and the AGO-B group contains the C. elegans proteins ALG-1, ALG-2, and HPO-24. The PIWI-like group contains ERGO-1, RDE-1, PRG-1, and PRG-2. The different WAGO groups contain WAGO-10, WAGO-11, HRDE-1, C14B1.7 and NRDE-3 (WAGO-A); CSR-1 and C04F12.1 (WAGO-B); SAGO-1, SAGO-2 and PPW-1 (WAGO-C); WAGO-1, WAGO-2, WAGO-4, WAGO-5, PPW-2, and C06A1.4 (WAGO-D); no Caenorhabditis WAGO’s (WAGO-E).

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