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RNA

processing
Gene$c flow

Central Dogma of life

gene

Google images
What is a Gene ?

A gene commonly is defined as the en#re


nucleic acid sequence that is necessary for the
synthesis of a func/onal product (Protein or
RNA).

Gene is DNA but all DNA is not gene


In humans, 90% of DNA do not code for any protein

Genome : Total gene$c content of the cell or organism



Genome size vs Organism complexity

•  C- Value paradox: Eukaryotic


genome size does not correlate
with organism complexity !

•  Genomes contain DNA other


than for genetic information!
•  Repetitive DNA

•  How can you explain this


complexity paradox?!
!

Nina V. Fedoroff. Science 09 Nov 2012: Vol. 338, Issue 6108, pp. 758-767
Structure of gene

§  Exons are coding regions of the nucleo$de sequence


responsible for the protein synthesis.

§  Exons and Introns both are copied into RNAs by transcrip$on.

§  Intron sequences do not encode proteins and are removed


by a process called splicing.
Any difference ?
Processing

RNA processing

•  5’ Capping

•  RNA splicing

•  3’ Polyadenyla$on
Capping
•  The 5ʹ end of the new RNA molecule is modified
by addi$on of a cap that consists of a modified
guanine nucleo$de
phosphatase

•  Three enzymes, ac$ng in succession perform


the capping reac$on:
guanyl transferase

–  A phosphatase removes a phosphate from the 5ʹ end


of the nascent RNA,
–  A guanyl transferase adds a GMP
–  A methyl transferase adds a methyl group to the
guanosine methyl transferase

•  The 5ʹ-methyl cap dis$nguish mRNAs from the other types


of RNA molecules present in the cell.
•  The 5ʹ-methyl cap also has an important role in the
transla$on
RNA splicing

GU AG

GU AG
With the par$cipa$on of U5, the 3ʹ end of the
intron is brought into proximity, cut, and joined to
the 5ʹ end.

U5 snRNP

The bonding of the guanine and adenine bases


takes place via a chemical reac$on known
as transesterifica$on, in which a hydroxyl (OH)
group on a carbon atom of the adenine "aZacks"
the bond of the guanine nucleo$de at the splice
site. The guanine residue is thus cleaved from the
RNA strand and forms a new bond with the
G adenine.
Possible explanaGons
•  Allows alterna$ve splicing

Google image
Advantages of alterna$ve splicing
•  Alterna$ve splicing produces proteins with different biological
func$ons, from the same gene

•  Humans have ~ 30,000 genes. But the current data revealed ~


30,000 proteins expressed in 30 cell types / 200.

•  Current research suggests that approximately 95% of


mul$exon genes in the human genome may undergo
alterna$ve splicing.

Dscam gene: 38000 isoforms can potentially


be produced by alternative splicing.

Any links to C value paradox ?


Introns: The Func$onal Benefits of Introns in Genomes, Bong-Seok Jo and Sun Shim Choi, Genomics Inform. 2015 Dec; 13(4): 112–118.
•  Introns can be sources for new genes
PolyadenylaGon

•  An enzyme called poly-A polymerase (PAP) adds, one


at a $me, approximately 200 nucleo$des to the 3ʹ end

•  The nucleo$de precursor for these addi$ons is ATP


and the same type of 5ʹ-to-3ʹ bonds are formed

•  As the poly-A tail is synthesized, proteins called poly-A-


binding proteins assemble onto it and, by a poorly
understood mechanism, help determine the final
length of the tail.

Protects from enzymaGc degradaGon in cytoplasm


Export to cytoplasm

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