Host: Ditlev E. Brodersen and MBG

Molecular insights into the mRNA poly(A) tail machinery
Cytoplasmic shortening of mRNA poly(A) tails represses eukaryotic gene expression by inhibiting efficient translation and committing an mRNA to decay. This occurs in
gene- and context-dependent manners to allow transcript-specific control of poly(A) tail lengths.

Understanding how specific mRNAs are targeted for deadenylation has been a central question in the field of gene expression for many years. Specificity is achieved through RNA adaptors – RNA-binding proteins that recruit the CCR4-NOT deadenylase machinery to certain substrate mRNAs in a regulated manner to target specific transcripts for deadenylation.

Examples of RNA adapters are Pumilio/Puf proteins, TTP/tristetraprolin and the microRNA-induced silencing complex (miRISC).

On the other hand, the PAN2–PAN3 deadenylation complex is generally thought to act non-discriminately on long poly(A) tails. Still, the molecular mechanisms of specificity remain unclear in many cases. We use
structural biology and biochemical reconstitution to approach this problem.

We find that RNA adapters are much more widespread than previously thought. Second, we find that RNA adapters interact with CCR4-NOT via multivalent interactions with their intrinsically disordered regions (IDRs).

Finally, these interactions can be regulated to mediated tuning of deadenylation rate. Together, this contributes to the intricate regulation of gene expression.