Role of MIR-430 during Gastrulation
Antonio J. Giraldez 2010. microRNAs, the cell’s Nepenthe: clearing the past during the maternal-to-zygotic transition and cellular reprogramming. Curr Opin Genet Dev . 20(4): 369–375.
Bazzini AA, Lee MT, Giraldez AJ. 2012. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science. 336(6078):233-7.
Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF. 2006. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 312(5770):75-9.
Very briefly tell us a bit about yourself, your career path over the years, and specifically what brought you to begin working on microRNA regulation of early development?
Based on when miR-430 is first present in the zygote, what determines when miR-430 will start to minitor translation of mRNAs so that maternal mRNA is not degraded too early during development?
What are the different components in the RISC complex, and how are they expressed? How are they related to the earlier expression of MZdicer?
Is it yet understood how mRNA targets are differentiated? For example, how is it that adipor1 is not deadenylated at 6 hpf and rhotekin is?
For your standard of what it means for an mRNA to be regulated by miR-430, why was two fold considered “regulated”?
In the introduction, MZdicer mutants are “saved” by injection of processed miRNAs belonging to the miR-430 family.At what point must mutants receive this “boost” in order to reap the benefits? How late can it be introduced and still produce viable zebrafish as miR-430 is normally expressed at the onset of zygotic transcription?
What is the mechanism by which miR-430 slows down the start of translation? Why is the start of translation only slowed down and not stopped?
If the embryo still activates its zygotic patterning without miR-430, is the mixed maternal-zygotic state of the embryo resulting from the competition for translation between the maternal and zygotic mRNAs? Does the embryo further develop as more zygotic programs are activated, or it remains in this state?
Could you elaborate on the experimental defects and the connections you are making from those to specific candidates and look at the cell cycle controls in this transition period?
Your 2006 paper suggests that the target set of mRNAs of miR-430 is rapidly evolving. What, if any benefit, could this have on embryogenesis (instead of having a conserved set of targets)?.
In your 2006 article you stated that miR-430 is directly regulate hundreds of target mRNAs during early embryogenisis in vivo. There are also other targets not identified what approach would be better in finding these additional targets since in silico methods miight not be biologically relevant?
Was there any issue using an argonaut because pewee interacting RNAs also use those argonaut proteins??
You mentioned that ‘miR-430 and other miRNAs sharpen developmental transitions and counteract the formation of mixed states.’ This model is related to the role of miRNAs in disease. How does this mechanism account for the miRNA-mediated induction of cancer? Can you explain?
Has the time point where the zygotic genome is activated been identified in the human embryo? When in the stage of development does the human embryo undergo the transition of reducing reliance on maternal mRNA?