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|Title: ||Characterization of Argonaute-related small RNA pathways in Caenorhabditis elegans|
|Authors: ||Batista, Pedro Jorge de Oliveira Rodrigues|
|Advisor: ||Gomes, Rui Artur Paiva Loureiro, 1958-|
Mello, Craig C., 1960-
|Keywords: ||Caenorhabditis elegans|
Interferência de RNA
Polimerase de RNA
Teses de doutoramento - 2011
|Issue Date: ||2010|
|Abstract: ||In Small-RNA-mediated pathways, small RNAs engage a protein of the Argonaute
family and utilize base-pairing interactions to identify and regulate complementary
genetic information. My research has focused on understanding how diverse classes of
small RNAs in the model organism Caenorhabditis elegans interact with specific
members of the Argonaute protein family to carry out unique biological functions.
During RNA interference (RNAi), functionally and structurally distinct Argonaute
proteins act sequentially to silence target mRNAs. In the first step, the Argonaute RDE-1
interacts with primary siRNAs, and interaction of this complex with the target mRNA
triggers a secondary amplification step. In this second step, RNA dependent RNA
polymerases (RdRPs) use the targeted mRNA as a template to generate an abundant pool
of small RNAs (22G-RNAs), which interact multiple Argonaute proteins to mediate
Several endogenous small-RNA-mediated pathways are essential for germline
development. One of these pathways is required for chromosome segregation and relies
exclusively on the Argonaute CSR-1, which utilizes 22G-RNAs generated from proteincoding
genes to promote the proper organization of chromatin domains. A distinct 22GRNA
germline pathway utilizes ‘aberrant’ RNAs as templates and is essential in
maintaining genome stability.
Proper germline development also requires the 21U-RNA class of small RNAs.
21U-RNAs specifically interact with the Piwi Argonaute PRG-1, thus establishing 21URNAs
as members of the piRNA family, which is important for germline integrity in all
metazoans. With only one known exception, 21U-RNAs fail to exhibit sequence
complementarity or evidence for direct regulation of other expressed sequences.
We now appreciate that the extent and means of small RNA regulation is much greater than we initially expected. My studies have contributed to the emerging theme
that small RNA pathways function on a genome-wide scale, to regulate many aspects of
cell biology and organismal homeostasis, from chromosome structure to gene expression.|
|Description: ||Tese de doutoramento, Biologia (Genética), Universidade de Lisboa, Faculdade de Ciências, 2011|
|Appears in Collections:||FC - Teses de Doutoramento|
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