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PROIECT ANTI-EDITARE

MICRO-ARN
CU SCOP TERAPEUTIC
Adenosine deaminases that act on RNA (ADARs) are
RNA-editing enzymes that deaminate adenosines to
create inosines in double-strandedRNA (dsRNA)
MicroRNAs were discovered in 1993 by Victor Ambros,
Rosalind Lee and Rhonda Feinbaum during a study of
the gene lin-14 in C. elegans development.[2]

Functiile micro ARN
si implicatii terapeutice
Micro-Rna-urile sunt fragmente mici de aproximativ 20-25 de
nucleotide prezente in celule in mii de tipuri diferite.
functia de intrerupatori de molecule in circuitele aflate la baza
functiilor celulare normale si patologice, sunt studii care vor putea cu
adevarat revolutiona modul de dezvoltare a viitoarelor terapii pentru
tumori - dupa Enrico Garaci, presedintele ISS-Italia-
transcriptional and post-transcriptional regulation of gene
expression (1)
animal miRNAs are able to recognize their target mRNAs by as little
as 6-8 nucleotides (the seed region) at the 5' end of an animal
miRNA.[3] Combinatorial regulation is a feature of miRNA
regulation. A given miRNA may have multiple different mRNA
targets, and a given target might similarly be targeted by multiple
miRNAs.[4][5]


Micro-ARN-urile din genomul uman
The human genome may encode over
1000 miRNAs, which may target about
60% of mammalian genes and are
abundant in many human cell types.


SCOPUL EXPERIMENTULUI

Metilarea la nivelul 2-O-riboza Adenina de pe
375 micro-ARN cu scopul de a inhiba procesul
de editare.
Editarea excesiva, in conditiile de stres oxidativ
de la nivelul 375 micro-ARN este implicat in
patogeneza T2D (6).
Procesul de editare este cauztat de catre ADAR
(Adenozin dezaminaza) prin dezaminarea
Adenozinei cu obtinera de Inozina (ce leaga
Citozina inloc de Uracil).
Proiect de inhibare ADAR
Metilarea Adenozinei din 2' riboza de pe
micro-RNA
Bibliografie
1. Chen, Kevin; Rajewsky, Nikolaus (2007). "The evolution of gene
regulation by transcription factors and microRNAs". Nature Reviews
Genetics 8 (2): 93103. doi:10.1038/nrg1990
2. Lee RC, Feinbaum RL, Ambros V (December 1993). "The C.
elegans heterochronic gene lin-4 encodes small RNAs with
antisense complementarity to lin-14". Cell 75 (5): 84354.
doi:10.1016/0092-8674(93)90529-Y. PMID 8252621.
3. Lewis BP, Shih IH, Jones-Rhoades M, Bartel DP, Burge CB
(2003). "Prediction of Mammalian MicroRNA Targets". Cell 115 (7):
787798. doi:10.1016/S0092-8674(03)01018-3. PMID 14697198.
4. Rajewsky, Nikolaus. "microRNA target predictions in animals".
Nature Genetics 38 (6s): S8S13. doi:10.1038/ng1798
5. Krek, Azra; Grn, Dominic; Poy, Matthew N; Wolf, Rachel;
Rosenberg, Lauren; Epstein, Eric J; MacMenamin, Philip; da
Piedade, Isabelle; Gunsalus, Kristin C; Stoffel, Markus; Rajewsky,
Nikolaus. "Combinatorial microRNA target predictions". Nature
Genetics 37 (5): 495500. doi:10.1038/ng1536. PMID 15806104.
6. Baran-Gale J, Fannin EE, Kurtz CL, Sethupathy P. PLoS One.
Beta cell 5'-shifted isomiRs are candidate regulatory hubs in
type 2 diabetes. 2013 Sep 9;8(9):e73240.