Eukaryotic genome structure and mRNA processing

Eukaryotic Gene

• Distal control elements

• Proximal control elements

• Promoter

• Gene (Exon + introns)

• Poly A sequences

• Terminator

Eukaryotic mRNA

• 5’Cap

• 5’UTR (Untranslated region)

• Coding segment

• 3’UTR (Untranslated region)

• Poly a tail

5′ cap

5′ end receives a modified guanine nucleotide

ribosomes bind the cap and scan to find the first AUG downstream

facilitate the export of mRNA to the cytoplasm, protect mRNA from hydrolytic enzymes, help ribosomes attach to the 5′ end; quality control (only capped mRNAs should be translated)

poly-A tail

3’ end modification; 50-250 adenine nucleotides

facilitate the export of mRNA to the cytoplasm, protect mRNA from hydrolytic enzymes

capping enzyme

adds 5’ cap

Splicing

Only some of the gene codes for protein: the rest needs to be removed before it is exported to the cytoplasm for translation

exons

coding regions

exons = 1 + introns

introns

non-coding regions

spliceosomes

remove introns; control RNAs; join together exons

Differential gene expression

There are over 200 different cell types in your body; all cells in your body have the same genetic information

Stages in gene expression that can be regulated

• Chromatin modifications

• Transcription initiation

• RNA processing

• RNA transport

• Translation

• Posttranslational modifications

DNA methylation

represses transcription

Euchromatin

transcription possible; active/open chromatin; unmethylated cytosines; acetylated histones

Heterochromatin

transcription impeded; silent/condensed chromatin; methylated cytosines; deacetylated histones

Histone acetyltransferases (HATs)

acetylate histones by attaching acetyl groups to an amino acid in a histone tail; open up the chromatin structure, promoting the initiation of transcription

epigenetic information

heritable without changing the DNA sequence

ex. histone and chromatin modifications

General transcription factors

bind to the promoter of all genes

in eukaryotes; each gene has it’s own promoter

Specific transcription factors

bind to enhancer elements

ex. activators, repressors

Modular interactions

allow different transcription factors to recruit the same proteins to different DNA sequences

DNA binding domain

confers sequence-specific DNA binding

Activation domain

interacts with other proteins

e.g. HATs, chromatin remodelers, general transcription factors, mediator proteins

Alternative splicing

Different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns; significantly expand the repertoire of a eukaryotic genome; It is a proposed explanation for the surprisingly low number of genes in the human genome; More than 90% of the human protein-coding genes undergo alternative splicing

isoform

a member of a set of highly similar proteins that originate from a single gene or gene family