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RNA-BASED SYNTHETIC

BIOLOGY
Central Dogma of Molecular Biology?
The central dogma of molecular biology
deals with the detailed residue-byresidue
transfer
of
sequential
information.
It
states
that
such
information cannot be transferred back
from protein to either protein or nucleic
acid. Francis Crick, 1970

1953 Watson, Crick, Franklin and Wilkins discover the 3D structure of


DNA

Non-coding RNA or ncRNA

tRNA non-coding RNA but extremely related with the central dogma
rRNA non-coding RNA but extremely related with the central dogma
snRNA small nuclear RNA

<200bp length.
Five important members: U1, U2, U4, U5 and U6.
Together with some peptides they form the spliceosome, a RNP directly
responsible for mRNA processing through mRNA splicing.

RNA splicing by the spliceosome

Self-splicing introns

snoRNA small nucleolar RNAs

They are guide RNA for the modification of others RNA molecules.
Hundreds of different snoRNAs.
Responsible for rRNA, tRNA and snRNA chemical modifications.
These modifications include methylation and pseudouridylation.

All of this types of RNA are very dogmatic


sRNA (asRNA) small RNA or asRNA (antisense RNA)

miRNA microRNA

Discovered by Victor Ambros in 1993 in C. elegans.


Little ssRNA (22nt) that, when loaded into Argonaute protein, are
capable of silencing gene expression.
In animals, plants and some viruses.
Human genome codes for >1000 miRNAs.
>50% of mammal protein coding genes are regulated by miRNA.

Imperfect stem loop structures


miRNA:

Endogenously produced by genes.


Implied in gene regulation.
Translational repression.
Imperfect stem loop structures and imperfect matching with target RNA.
Interferes with protein translation.

siRNA small interfering RNA

Related with RNAi response.


Triggered by 500bp fragments of dsRNA.
The trigger is processed into pieces of 21-25 nt: siRNA.
Shared proteins with miRNA.
Perfect match with target RNA.
Induces mRNA cleavage.

These ncRNA are not directly related with the central dogma. They are
related with regulation (sRNA(asRNA) and miRNA) and defense (siRNA)

1. Interferon is a protein, not an RNA related


with RNAi.
2. Tetrahymena is a ciliated protozoan.
3. RISC stands for RNA-Induced Silencing
Complex.
4. Did you write where miRNAs usually
interact? Where?

Enzymes:

Ribozymes

Discovered in the 80s, ribozymes are RNAs with enzymatic capabilities.


There are not too much naturally occurring ribozymes.
Ribozymes constitute a supporting evidence for the so-called RNA world
hypothesis (do you know what is this?).
Most ubiquitous ribozymes require proteins for efficient catalysis in vivo.
True protein-devoid ribozymes have been discovered only in viral-like
sources.

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