Sandbox RDE-1

From Proteopedia

Introduction

The rde-1 gene is a member of the Argonaute gene family. Proteins from "Argonaute" family form an evolutionarily conserved family whose members silence gene expression in pathways such as RNA interference (RNAi). Argonaute family proteins can be divided into two types, AGO and PIWI proteins, depending on the small RNA they bonded to. Both types of Argonaute proteins bind 21–35 nucleotide-long small RNA guides whose sequence identifies the genes to be silenced. ^[1] RDE-1 (RNAi-DEfective 1), a primary Argonaute protein, is required for RNA-mediated interference in Caenorhabditis elegans; thus, it is also known as RNAi promoting factor. Its gene locus was first characterized in C. elegans mutants resistant to RNAi, and was found to be a member of the PIWI gene family that includes plant, Drosophila, and vertebrate homologs. ^[2]

Structure

Canonical Argonaute proteins possess three primary domains forming a crescent-shaped base: the PAZ, MID, and PIWI domains. PAZ and MID orient and anchor the double-stranded siRNA by binding to the 3’ and 5’ termini, respectively, leaving the internal nucleotides accessible for base pairing. The PIWI domain folds into an RNase H-like structure, and contains the conserved catalytic triad “DDH” (two aspartate residues, one histidine residue). The crystal structure of RDE-1 has not been formally elucidated, but can be assumed to closely resemble its human homologs. RDE-1 protein consists of 1020 amino acids. ^[3] The PAZ domain contain about 110 amino acids, and the PIWI domain consists of 300 amino acids. ^[4]

Importance/Function

Proposed RNAi pathway for exogenous trigger dsRNA in C. elegans. ^[5]

Disease

Relevance

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References

1. ↑ https://www.sciencedirect.com/science/article/pii/S0960982211005471
2. ↑ Tabara, H.; Sarkissian, M.; Kelly, W. G.; Fleenor, J.; Grishok, A.; Timmons, L.; Fire, A.; & Mello, C. C. (Oct 1999). "The rde-1 gene, RNA interference and transposon silencing in C. elegans". Cell. 99 (2): 123–32. doi:10.1016/S0092-8674(00)81644-X. PMID 10535731
3. ↑ Tabara, H.; Sarkissian, M.; Kelly, W. G.; Fleenor, J.; Grishok, A.; Timmons, L.; Fire, A.; & Mello, C. C. (Oct 1999). "The rde-1 gene, RNA interference and transposon silencing in C. elegans". Cell. 99 (2): 123–32. doi:10.1016/S0092-8674(00)81644-X. PMID 10535731
4. ↑ https://www.sciencedirect.com/science/article/pii/S0968000400016418
5. ↑ https://en.wikipedia.org/wiki/RDE-1#/media/File:Exogenous_RNAi_Pathway_in_C._elegans,_edited.svg