How does normal mRNA escape from cleavage by dicer? - (Mar/04/2006 )

Hello,
Since mammalian mRNA normally fold up into higher order structures and contain many of the same hairpin stems and loops that miRNA has, how are they prevented from being treated as miRNA?

---

If an mRNA can form hairpin stem-loop structurre, I don't see the reason why dicer doesn't dice it. Perheps this is a naturally occuring regulatory mechanism and needs further investigation.

---

I was thinking that as well but it would mean almost all RNAs would be cleaved by dicer. tRNA and rRNA have well documented stem-loop structures as well as many mRNAs such as histone mRNA with the stem-loop in their 3'UTR for example. In fact you can fold almost any mRNA up using a thermodynamic prediction program such as MFOLD and you'll get a neat little diagram structure loaded with loops and stems. I haven't been able to find much info regarding how dicer discriminates between double stranded endo/exo-genous siRNA and pre-miRNA versus that of every other folded up RNA in the cell. Or maybe it's a question of how these other RNAs prevent themselves from interacting and getting cleaved by dicer.

---

You might forget here that DICER needs a 2 bp overhang at 3' end to cleave efficiently, if the PAZ domain isn't connecting to that cleavage is unlikely.

---

actually, DICER cleaves the hairpin structure, generating 5' phosphate and 2bp 3'overhang...
RISC needs that structure to cleaves the RNA

---

Actually the 3' end still needs a 2bp for DICER, but DROSHA cuts without the 3' 2Bp.
DICER tends to just walk forward so to say and generates siRNA as long as it has a double stranded substrate with the overhang, but still PAZ needs to bind this overhang.

---