The long and the short of RNA export

The RNA polymerase II transcriptional machinery produces both protein-encoding messenger RNA (mRNA) and considerably shorter molecules called spliceosomal U RNA (U snRNA). Both RNAs bind the cap-binding complex (CBC) as a prelude to export to the cytoplasm. However, mRNAs and U snRNAs are subsequently escorted from the nucleus by different cofactors.

Kyoto University researcher Mutsuhito Ohno and colleagues recently revealed how this sorting occurs¹. Previous studies had revealed that RNA length is a key determinant of whether or not newly synthesized RNAs bind to PHAX, a protein that interacts with both RNA and CBC and thereby facilitates U snRNA export. However, the researchers observed that PHAX can successfully bind both short and long RNAs in in vitro experiments.

This changed when they added cellular extracts to the mix. Closer analysis enabled the researchers to identify complexes of proteins — hnRNP C1 and C2 — as the key determinant of whether or not PHAX binds a given RNA. These complexes do not bind to RNAs shorter than 2–300 nucleotides, such as U snRNAs. mRNAs are typically far longer than this, however, and hnRNP C1/C2 interacts with these nascent RNAs and associated CBC molecules. This binding in turn prevents interaction with PHAX, and thereby shunts long RNAs into the mRNA export pathway.