Tuesday, August 28, 2007

Impressions from Cold Spring Harbor mRNA processing Meeting

Every 2 years scientists from around the world gather in Cold Spring Harbor, New York, to discuss the latest developments in Eukaryotic mRNA Processing.

It was my second time. Four years ago, not long after RNAi had been discovered to operate in humans, I presented some data relating to the effect of Dicer knockdown on intergenic transcript abundance in an RNAi session. This time, there was no RNAi session, not even as part of the RNA turnover session. Instead, the Meeting focussed on the more traditional topics of the field, particularly mRNA splicing. This development illustrates how fast RNAi has grown, not only in numbers, but also in diversity of research areas so that it is not possible any more to accommodate it in one or two sessions alone.

This is unfortunate as I think both fields have a lot to learn from each other. One example where such an information exchange would be fruitful is in the rapidly growing application of high-throughput cloning and sequencing techniques for the identification of RNA populations. Specifically, I have not seen the CLIP technique, which allows the identification of RNAs bound to a protein of interest, being widely applied in the RNAi arena.

Similarly, I feel that the potential of targeting misspliced RNAs with RNAi for therapy is underappreciated due to a lack of sufficient communication. Almost one third of all human disease is thought to be due to splicing defects and I could well imagine RNAi therapeutics specifically targeting misspliced RNAs that cause pathogenic gain-of-functions. Type 1 myotonic dystrophy is another condition where a toxic RNA causes a disease that is essentially due to splicing mis-regulation. Importantly, Langlois and colleagues have shown before that it is possible to down-regulate the underlying mutated DMPK mRNA by DNA-directed RNAi (J Biol Chem. 2005 Apr 29; 280:16949-54).

However, no matter where conference organizers draw the line, they will have to recognize that RNAi and eukaryotic mRNA processing are intimately intertwined. I hope this realization will help speed up research in microRNA biogenesis for example where the nuclear events in particular remain surprisingly understudied. This cannot but change given that many of the leading scientists in the RNAi field have grown up studying traditional RNA processing and almost everybody at the conference has successfully used RNAi in their research. By the way, only once was it mentioned that somebody failed with their knockdown experiments, and, after much trepidation, it turned out that this person had been using morpholino antisense oligos, not RNAi.


Paul said...
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Paul said...

If you are willing to deal with off-target effects, immune responses in vivo, the fact that it works very poorly in zebrafish compared to Morpholinos, and the fact that you can't perform exon skipping like you can with Morpholinos (a viable treatment for several diseases), then by all means RNAi is great!
Paul Morcos

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