Science 335, 1643–1646 (2012)

RNAs are synthesized by common transcriptional pathways but are trafficked to their cellular destinations by various RNA transport machineries. For instance, both spliceosomal U small nuclear RNAs (snRNAs) and mRNAs are transcribed by RNA polymerase II and undergo 5′-terminal capping, which is recognized by cap-binding complex (CBC). Their journeys then diverge, with snRNA trafficking in the nucleus being initiated by the phosphorylated adapter RNA export protein (PHAX) and mRNA export out of the nucleus being coordinated by RNA-binding adaptors such as Aly/REF. Previous studies have suggested that the transcript's length—with snRNAs typically being shorter than mRNAs—rather than its sequence controls the choice of RNA transport pathway. McCloskey et al. now identify a heterogeneous nuclear ribonucleoprotein (hnRNP) that serves as a 'molecular ruler' for RNA transport pathway selection. Using a biochemical approach, the authors purified a heterotetrameric complex of hnRNP C1/C2 (hnRNP C), which simultaneously binds larger RNAs (>200–300 nucleotides) and a subunit of their associated CBCs, an interaction that blocks PHAX binding. This assembly was validated in cells by showing that hnRNP C knockdown led to enhanced PHAX binding to RNA–CBC complexes and increased nuclear retention of mRNA constructs without affecting pre-mRNA splicing. Taken together, these observations suggest a model in which hnRNP C selectively binds longer RNAs and shunts them toward mRNA export pathways.