Mostly Biomathematics Lunchtime Seminar

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The fast search for an RNA target within the complex soup of the cell

Speaker: Ofer Kimchi, Courant Institute of Mathematical Sciences

Location: Warren Weaver Hall 1314

Date: Tuesday, September 29, 2026, 12:45 p.m.

Synopsis:

A typical bacterial cell has O(10^5) RNA molecules of widely varying lengths. In this context, the RNA-binding protein CRISPR-Cas13 must be able to locate one particular location on one particular phage RNA---and it must do so within the time constraint of phage infection. How? The answer lies in the idea that reducing the dimensionality of the search speeds up the search process. For example, transcription factors have been known since the 1970's to speed up their search for their DNA binding site beyond the 3D diffusion limit by combining 3D and 1D diffusion. I will explain why this search strategy is insufficient for a search in RNA-space, and describe modeling work and experimental evidence demonstrating that Cas13 uses a different strategy for its search: intersegmental transfers (ITs), which leverage the RNA's own internal dynamics for the search. I will reformulate ITs as a reduction in dimensionality to fractional dimension, and show that ITs enable RNA-binding proteins such as Cas13 to create a "length filter": quickly dissociating from short non-target RNAs while thoroughly searching long RNAs more likely to be the target.