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Diploma of Thorough Studies
« Biology of the Blood
cells »
TLS, a protein of the spliceosome, is implied in the mechanism
of action of the rétinoïque acid
through the regulations
post-transcriptionnelle
and transcriptionnelle
Eric Corvec
University Paris 7 Denis Diderot
July 2002
Cellular laboratory of Biology
Hématopoïétique
EMI 00-03, Univ. Paris 7 EA 316, Saint-Louis
UF474
University institute of Hematology, Saint-Louis
Hospital
75475 Paris Cedex 10
Director of the laboratory and Master of training
course
Christine Chomienne
Laurent Delva
I cordially thank Christine Chomienne for having
allowed myself to carry out this DEA.
I in particular thank Laurent Delva who me provided
assistance and councils, and without which this work could not have been
possible.
I thank Gilles Despouy for his moral and scientific
support.
I thank Nicole Balitrand for his advised
councils.
I thank Sylvie Deshaie for all that it brought to me
during the year.
Thank you friendly in Alexandra Mazharian for her
good mood.
Lastly, I would like to thank all the team for the
LBCH for their reception and their sympathy.
SUMMARY
The regulations transcriptionnelle and post-transcriptionnelle
are strongly implied in the diversification of the proteinic expression.
The fact that TLS is surexprimée in 60% of the LAM and
that it interacts with RXR, one of the principal partners of the RANC, enables
us to put forth the assumption that TLS would be related to the way of
indication of AR in the hematopoietic cells. TLS, a protein
ubiquitairement expressed, intervenes in many molecular mechanisms. Many
studies show that it is related to the transciptionnelle machinery as well as
with that of the épissage.
We initiated the study of the action of TLS and AR on the
transcriptionnelle activity in myeloblastic cells HL-60. The membership of TLS
to the complex transcriptionnel of the receivers to the rétinoïque
acid is evaluated by the technique of delay on freezing with the two nuclear
receivers with the rétinoïdes (RAR and RXR). Moreover, the role of
TLS and AR on the épissage was studied by a technique of analysis in
vivo, on the alternate épissage into 5 ' of minigene E1A in the
hematopoietic cells K562 in absence or in the presence of
rétinoïque acid.
Our work made it possible to characterize a role of
Co-activator of the transcription by the receivers with the
rétinoïdes in the presence of rétinoïque acid in the
cells HL-60 and Cos-6, its membership of the RANC and a role of factor of
épissage supporting the selection of distal site 5 ' of épissage
of minigene E1A in the cells myéloïdes K562. We showed that TLS
also acts with the way of indication of the rétinoïdes which
accentuate the effects observed of TLS on the épissage.
The rétinoïque acid is thus implied at the same
time in the transcriptome and the spliceosome through TLS. Thus, it is the
first time that the way of indication of the hormones is implied in the
épissage and the transcription through a factor of épissage.
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