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1993
Nature 2010
morphology
brachyury
Embryo 7.5
Oct 4
Components:
Possible interplay between RNA binding proteins and microribonucleoproteins interacting with the mRNAs 3 UTR
MicroRNA editing
Editing is defined as a post-trascriptional change of RNA sequences by
deamination of adenosine (A) to inosine (I), altering the base-pairing and
structural properties of the transcript.
Editing of miRNA transcripts by ADARs (adenosine deaminases acting on RNA)
was first described for miR-22 followed by miR-151, miR-197, miR-223,
miR-376a..
Consequences.
In primiR-142, A-to-I editing inhibits its cleavage by endonuclease Drosha and
results in its degradation by ribonuclease Tudor-SN, which preferentially cleaves
double-stranded RNA containing inosine-uracil pairs.
In prmiR-151 editing abolishes its cleavage by Dicer in the cytoplasm.
In primiR-376 a single A-to-I change redirects the mature miRNA to a new target,
resulting in altered protein expression in mice.
To be established.
Predominantly nuclear or cytoplasmic events?
Do they occur on the primiR or in the premiR?
Some miRNAs require additional specificity factors (for example RNA helicases
p68 and p72) for efficient cleavage
Splicing can replace Drosha processing if the released and debranched intron
(mirtron) has the length and haitpin structure of a pre-miRNA
MicroRNA identification
Experimental approaches:
Cloning and sequecing endogenous small RNAs of 21-25
bp long (on the basis of characteristics of Dicer cleavage,
temporally and spatially regulated expression and, in many
cases, evolutionary conservation)
Bioinformatic predictions (on the basis of pre-miRNA
hairpin structures and sequence conservation throughout
evolution i.e. miRScan and miRSeeker )
microRNA Registry (more than 500 in human genome)
(http://microRNA.sanger.ac.uk)
Flow-based/Liquid-phase array
Increse specificity
Higher sensitivity
Technically demanding
1. Chromosomal abnormality
2. Epigenetic changes
3. Mutations and SNPs
4. Defects in the miRNA biogenesis machinery
Lung cancer patients carrying the hsa-mir-196a2 rs11614913 CC genotype had a lower
survival than the patients carrying TT/CT genotypes, especially among stage I/II
patients.
miR-106b-25