Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway
Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is involved in microRNA silencing, another process implicated in CD pathogenesis. MicroRNAs are short non-coding...
Main Author: | |
---|---|
Other Authors: | |
Language: | en_ca |
Published: |
2012
|
Subjects: | |
Online Access: | http://hdl.handle.net/1807/42408 |
id |
ndltd-LACETR-oai-collectionscanada.gc.ca-OTU.1807-42408 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-LACETR-oai-collectionscanada.gc.ca-OTU.1807-424082013-12-06T03:37:54ZAutophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing PathwaySibony, MichalAutophagymicroRNACrohn's DiseaseArgonaute 2RNA-induced Silencing Complex0719Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is involved in microRNA silencing, another process implicated in CD pathogenesis. MicroRNAs are short non-coding RNAs that are loaded onto RNA-induced silencing complex (RISC) and promote degradation and/or repress translation of target mRNAs. RISC formation and turnover occurs on endosomal membranes. Since autophagosomes and endosomes are closely related and RISC components are downstream effectors of microRNA silencing, I hypothesized that autophagy affects RISC, hence modulates microRNA expression. Using immunoblotting and immunofluorescence, I showed that Ago2, a critical component of RISC, is increased in cells with defective autophagy. Using microarray technology, I discovered 5 microRNAs that are differentially expressed in these cells. Taken together, my results propose a compelling mechanism by which autophagy regulates Ago2, thereby affects miRNA expression, which is implicated in the development of CD.Jones, Nicola L.Silverberg, Mark2012-112013-11-15T18:10:02ZWITHHELD_ONE_YEAR2013-11-15T18:10:02Z2013-11-15Thesishttp://hdl.handle.net/1807/42408en_ca |
collection |
NDLTD |
language |
en_ca |
sources |
NDLTD |
topic |
Autophagy microRNA Crohn's Disease Argonaute 2 RNA-induced Silencing Complex 0719 |
spellingShingle |
Autophagy microRNA Crohn's Disease Argonaute 2 RNA-induced Silencing Complex 0719 Sibony, Michal Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
description |
Genome-wide association studies have implicated autophagy in Crohn’s Disease (CD) pathogenesis. The functional relevance of autophagy in CD remains unknown. I hypothesized that autophagy is involved in microRNA silencing, another process implicated in CD pathogenesis. MicroRNAs are short non-coding RNAs that are loaded onto RNA-induced silencing complex (RISC) and promote degradation and/or repress translation of target mRNAs. RISC formation and turnover occurs on endosomal membranes. Since autophagosomes and endosomes are closely related and RISC components are downstream effectors of microRNA silencing, I hypothesized that autophagy affects RISC, hence modulates microRNA expression. Using immunoblotting and immunofluorescence, I showed that Ago2, a critical component of RISC, is increased in cells with defective autophagy. Using microarray technology, I discovered 5 microRNAs that are differentially expressed in these cells. Taken together, my results propose a compelling mechanism by which autophagy regulates Ago2, thereby affects miRNA expression, which is implicated in the development of CD. |
author2 |
Jones, Nicola L. |
author_facet |
Jones, Nicola L. Sibony, Michal |
author |
Sibony, Michal |
author_sort |
Sibony, Michal |
title |
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
title_short |
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
title_full |
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
title_fullStr |
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
title_full_unstemmed |
Autophagy Regulates Expression of Argonaute 2, a Critical Regulator of the MicroRNA Silencing Pathway |
title_sort |
autophagy regulates expression of argonaute 2, a critical regulator of the microrna silencing pathway |
publishDate |
2012 |
url |
http://hdl.handle.net/1807/42408 |
work_keys_str_mv |
AT sibonymichal autophagyregulatesexpressionofargonaute2acriticalregulatorofthemicrornasilencingpathway |
_version_ |
1716616380585869312 |