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RNA processing

Gene$c flow

Central Dogma of life

gene
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

Genome size vs Organism complexity • C- Value paradox: Eukaryotic genome size does not correlate with

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

Structure of gene §   Exons are coding regions of the nucleo$de sequence responsible for the

§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 ?

Any difference ?

Processing

Processing RNA processing •   5’ Capping •   RNA splicing •   3’ Polyadenyla$on

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

Three enzymes , ac$ng in succession perform the capping reac$on:

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

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

phosphatase guanyl transferase methyl transferase
phosphatase
guanyl transferase
methyl transferase

GU

GU

GU GU RNA splicing AG AG

RNA splicing

AG

AG

G

U5 snRNP

G U5 snRNP With the par$cipa$on of U5, the 3ʹ end of the intron is brought

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

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 adenine.

Possible explanaGons Allows alterna$ve splicing

Possible explanaGons •   Allows alterna$ve splicing Google image

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.

genes in the human genome may undergo alterna$ve splicing. Dscam gene: 38000 isoforms can potentially be

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

Export to cytoplasm