The RNA-binding protein HuR controls key cellular processes by binding target
mRNAs and regulating them at
various
post-transcriptional levels. HuR
can function as
an
Internal
Ribosome
Entry
Site (IRES)
trans-acting factor
that
regulates the IRES-mediated
translation of XIAP.
Since
XIAP and Bcl-xL
expression was reported to be co-regulated, we
investigated whether
HuR
is also a
regulat
or of Bcl-xL expression. We found that HuR binds
the 3’end of the Bcl-xL 5’UTR
in-vitro. In U2OS cells, we showed that loss of HuR by
siRNA significantly increased Bcl-xL protein expression
while
Bcl-2 and Mcl-1 levels
remained unchanged. We found that
the HuR-dependent
Bcl-xL
increase was
through
translation,
shown by polysome
profiling.
Possible transcriptional, stability
and splicing
changes were eliminated.
At the physiological level HuR levels did not impact cell survival
but altered mitochondrial morphology,
partially through Bcl-xL.
Thus, HuR may be involved
in maintaining proper mitochondrial
function
by controlling Bcl-xL expression.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/23206 |
| Date | January 2012 |
| Creators | Durie, Danielle |
| Contributors | Holcik, Martin |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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