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Gene Expression in Eukaryotes:

Transcription

Maria Milagros U. Magat, MD,


MEM,FPPS,FPAPP
Facilitator
5/17/17
Lecture objectives:

At the end of the lecture, the student is able to:


1.Compare and contrast: replication & transcription;
prokaryotic & eukaryotic transcription; types of RNAP
2. Summarize: steps in eukaryotic RNA synthesis, co-
and post - transcriptional modifications, export to
cytoplasm, and decay
3. Conclude how regulatory (including epigenetic)
mechanisms at the transcriptional level affect gene
expression of:
a. LDL-R b. glucokinase c. PEPCK d. apoB48 & apo100
4. Summarize the role of metformin in the regulation
of key processes in metabolism
Overview: eukaryotic RNA synthesis
Products of RNA polymerases

polymerase products
RNA polymerase I rRNA
RNA polymerase II mRNA + microRNA
RNA polymerase III tRNA + other small
RNA
Steps in RNA
synthesis
Initiation
Elongation
Termination
Co and post-transcriptional
processing
Eukaryotic RNA polymerase II

Stryer,6th ed
Overview:
Transcription

Clark, D. - Molecular
Biology,2013
mRNA synthesis
Initiation complex: assembly

Devlin,7th ed
Clark, D. - Molecular
Biology,2013
Harper, 29th ed
Initiation: mRNA promoter region

Clark, D. - Molecular
Biology,2013
mRNA synthesis
Initiation complex: assembly

Devlin,7th ed
Clark, D. - Molecular
Biology,2013
mRNA synthesis
Initiation complex: assembly

Clark, D. - Molecular
Biology,2013
mRNA synthesis
Initiation complex: assembly

Clark, D. - Molecular
Biology,2013
mRNA synthesis: Elongation

Clark, D. - Molecular
Biology,2013
mRNA synthesis: Elongation

* methylation of internal nucleotides

Marks ,4th ed
mRNA synthesis: cotranscriptional
modification
1. capping

Clark, D. - Molecular
Clark, D. - Molecular
Biology,2013
Biology,2013
mRNA synthesis: cotranscriptional modification
2. poly(A) tail

Clark, D. - Molecular
Biology,2013
mRNA synthesis: cotranscriptional
modification
3. splicing

Harper,29th ed

Clark, D. - Molecular
Biology,2013
mRNA synthesis: cotranscriptional
modification
3. splicing

Clark, D. - Molecular
Biology,2013
mRNA synthesis:
cotranscriptional
modification
3. splicing

Clark, D. - Molecular
Biology,2013
mRNA synthesis: post-transcriptional
modification

Secondary methylation- 2OH; N7 of


A
5UTRs; 3 UTRs: biologic relevance

Harper,29th ed
mRNA synthesis:
summary

Marks ,4th ed
rRNA synthesis: initiation step

Clark, D. - Molecular
Biology,2013
rRNA synthesis: post-transcriptional
modification

Devlin,7th ed
www.google images/rRNA
rRNA synthesis: post-transcriptional
modification

snoRNP
Methylation of ring N
Pseudouridine formation

Clark, D. - Molecular
Biology,2013
Devlin,7th ed
rRNA synthesis:
summary

Marks ,4th ed
tRNA synthesis: initiation step

Clark, D. - Molecular
Biology,2013
tRNA synthesis: post-transcriptional modification

Marks ,4th ed
tRNA synthesis: post-transcriptional modification

Clark, D. - Molecular
Biology,2013
tRNA synthesis:
summary

Marks ,4th ed
Export to cytoplasm

Devlin,7th ed
Clark, D. - Molecular
Biology,2013
Export to cytoplasm

Aminoacyl tRNA synthetase


RNP particles
P bodies
Harper,29th ed
Devlin,7th ed
RNA decay

Devlin,7th ed
Regulation
.Epigenetics: Chromatin remodelling
histone code - de/acetylation, **CH3,
***PO43-,ubiquitinated, sumoylated, deiminate
DP-ribosylated, isomerized
. Gene-specific transcription factors
. Alternative promoter sites
. RNA editing
Harper,29th ed
Marks ,4th ed

Devlin,7th ed
Clark, D. - Molecular
Biology,2013
Regulation of gene expression: Epigenetic mechanism

Clark, D. - Molecular
Biology,2013
Regulation of
gene expression:
Epigenetic
mechanisms

Clark, D. - Molecular
Biology,2013
Regulation of gene expression: Epigenetic mechanism

Clark, D. - Molecular
Biology,2013
Regulation: mRNA synthesis

Clark, D. - Molecular
Biology,2013
REGULATION of HMG CoA REDUCTASE
1. Transcriptional control

Marks ,4th ed
LDL-R synthesis (transcriptional
control)

Devlin,7th ed
Glucokinase: promoter sites

Harper,29th ed
Glucokinase: transcription factors

Harper,29th ed
apoB48 & apo B100

Clark, D. - Molecular
Biology,2013
PEPCK/ G6Pase synthesis (transcriptional
control

Lehninger 5ed
Summary: Regulation

www.cellsginalling.com

Marks, 4ed
MOA: Metformin

Marks,4th ed
In
summary:
1.Compared &contrasted: replication &
transcription; prokaryotic & eukaryotic
transcription; types of RNAP
2. Summarized: steps in eukaryotic RNA
synthesis, co- and post - transcriptional
modifications, export to cytoplasm, and decay
3. Concluded: regulatory (including epigenetic)
mechanisms at the transcriptional level affect
gene expression of: a. LDL-R b. glucokinase c.
PEPCK d. apoB48 & apo100
4. Summarized: role of metformin in the
regulation of key processes in metabolism

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