Tethered by monkeytail

IECB team leader Dr. Cameron Mackereth, through interdisciplinary research with the group of Sébastien Fribourg, discovers that Rna14p and Rna15p, two proteins which contribute to messenger RNA maturation in yeast, are tethered by cooperative folding of two peptides: the hinge domain and the monkeytail domain.

In cells, DNA is transcribed into mRNA in the nucleus, which is then exported to the cytoplasm to be translated into proteins. Several key events occur during the mRNA maturation process to turn the initial pre-mRNA transcript into a functional mRNA molecule.

Twenty years ago, Dr. Lionel Minvielle-Sébastia discovered certain yeast mutants with abnormal mRNA processing that made the cells unable to grow at raised temperatures. Two years ago, Dr. Cameron Mackereth, group leader at IECB, started a collaboration with IECB colleagues Maria Moreno Morcillo in Sébastien Fribourg group and Dr. Minvielle-Sébastia to study the structure of the proteins found to be mutated in the genetic screen. These proteins are part of a complex that is responsible for proper processing of pre-mRNA. Specifically, the complex helps with precise cleavage of the pre-mRNA at a specific site in the 3’-region, followed by polyadenylation and creation of the poly(A) tail important for mRNA function.

In the April 13 issue of Structure, they report their discovery that two proteins of this complex, Rna14p and Rna15p, are strongly connected via specific domains: the monkeytail domain from Rna14p and the hinge domain from Rna15p. These two peptides, which have no defined three-dimensional structure on their own, fold into a molecular embrace when they associate. They also found that the previously identified mutants specifically prevent formation of this protein tether and thus provides an atomic explanation for the observed processing defects. Based on sequence similarity, it appears that this critical link is also a component of the similar complex required for pre-mRNA processing in humans.

Moreno-Morcillo M., Minvielle-Sébastia L., Fribourg S., Mackereth C.D. (2011) Locked Tether Formation by Cooperative Folding of Rna14p Monkeytail and Rna15p Hinge Domains in the Yeast CF IA Complex. Structure, Apr 13;19(4):534-45.