Differential GENE

EXPRESSION
TRANSCRIPTIONAL REGULATION
RNA PROCESSING
TRANSLATIONAL REGULATION
TRANSCRIPTION

 The process by which a gene makes an RNA is called transcription.

 Gene is the DNA sequence which transcribes into RNA.
 If it is mRNA then it will undergo translation while there are genes that
transcribes just into tRNA and rRNA which became functional after some
processing.
 Transcription is carried out by general transcription factors(TF) which recruits the
transcriptional machinery into the correct place so that everything goes well.
Transcriptional Regulation

 Transcriptional regulation occurs via transcription factors that bind to short

control elements associated with the target genes and then interact with each other
and with the transcription initiation complex to increase or decrease the rate of
transcription of the target gene.
 Many transcription factors bind to control elements located upstream within a few
hundred base pairs of the protein-coding gene. The SP1 box and CAAT box are
examples of such regulatory elements found upstream of most protein-coding
genes, but some regulatory elements are associated with only a few genes and are
responsible for gene-specific transcriptional regulation (e.g. hormone response
elements).
Cis and trans ELEMENTS

 Transcription factors recognize and bind to short regulatory DNA sequences

(control elements) associated with the gene. These sequences are also called cis-
acting elements (or simply cis-elements) since they are on the same DNA
molecule as the gene being controlled (cis is Latin for ‘on this side’).
 The protein transcription factors that bind to these elements are also known as
trans-acting factors (or simply trans-factors) in that the genes encoding them can
be on different DNA molecules (i.e. on different chromosomes).
Enhancers

 Enhancers are positive transcriptional control elements typically

100–200 bp long that can be located either upstream or downstream
of the target gene, are active in either orientation, and can activate
transcription from the target gene even when located a long distance
away (sometimes 10–50 kb). The transcription factors bound to
these long-distance elements interact with the transcription initiation
complex by looping out of the DNA.
Enhancer looping
Multiple Domains of TFs

 Transcription factors that increase the rate of transcription usually have at least
two domains of protein structure, a DNA-binding domain that recognizes the
specific DNA control element to bind to, and an activation domain that interacts
with other transcription factors or the RNA polymerase. Many transcription
factors operate as dimers (homodimers or heterodimers) held together via
dimerization domains. Some transcription factors interact with small ligands via a
ligand-binding domain.
 A part of a polypeptide chain with a folded structure that does not depend for its
stability on any of the remaining parts of the protein is called domain.
 A domain substructure that occurs in many different proteins, often having some
characteristic amino acid sequences properties is called motif.
 (e.g., the helix-turn-helix motif in many DNA-recognition domains)
RNA SPLICING

 Genes with intervening sequences are called split genes.

 Gene contain two regions, i.e. coding as well as non-coding.
 The coding region of the gene is called exon.
 The non-coding region of the gene is called intron.
 The process by which the introns in the pre-mRNA are removed and the
remaining exons are ligated together is called RNA SPLICING.
 The exon-intron boundaries are marked by specific sequences.
RNA Splicing

In vertebrates this sequence is 5 -CURAY-3 where R is purine and Y

is pyrimidine (in yeast this sequence is 5 -UACUAAC-3 ).
MECHANISM
SPLICEOSOME
DIFFERENTIAL RNA processing

 Differential RNA processing is the splicing of mRNA precursors into messages

that specify different proteins by using different combinations of potential exons.
 For instance, If an mRNA precursor had five potential exons, one cell type might
use exons 1, 2, 4, and 5; a different cell type might use exons 1, 2, and 3; and yet
another cell type might use all five.
 Thus, a single gene can produce an entire family of proteins.
 The different proteins encoded by the same gene are called splicing isoforms of
the protein.
 A means of producing multiple different proteins from a single gene by splicing
together different sets of exons to generate different types of mRNAs is called
Alternative nRNA splicing.
Alternative splicing
Different ways to do A.splicing
Some explanation…

 The Bcl-x gene provides a good example of how alternative nRNA splicing can
make a huge difference in a protein’s function. If a particular DNA sequence is
used as an exon, the “large Bcl-X protein,” or Bcl-XL, is made. This protein
inhibits programmed cell death. If this sequence is seen as an intron, however, the
“small Bcl-X protein” (Bcl-XS) is made, and this protein induces cell death. Many
tumors have a higher than normal amount of Bcl-XL.
 In Drosophila there is Dscam gene which encodes a membrane adhesion protein
that prevents dendrites from the same neuron from interacting.
 Dscam contains 115 exons. Moreover, a dozen different adjacent DNA sequences
can be selected to be exon 4, and more than 30 mutually exclusive adjacent DNA
sequences can become exons 6 and 9, respectively.
DSCAM miracle!

 If all possible combinations of exons are used, this one gene can produce 38,016
different proteins.
UTR(UNTRANSLATED REGIONS)

5’ UTR starts from the cap to the first AUG codon and it is called leader
sequence while 3’ UTR starts from the termination codon such as UAA,
UAG,UGA to the poly A tail and it is also called trailer sequence.
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