Abstract
A 5′,7-methylguanosine cap is a quintessential feature of RNA polymerase II-transcribed RNAs, and a textbook aspect of co-transcriptional RNA processing. The cap is bound by the cap-binding complex (CBC), canonically consisting of nuclear cap-binding proteins 1 and 2 (NCBP1/2). Interest in the CBC has recently renewed due to its participation in RNA-fate decisions via interactions with RNA productive factors as well as with adapters of the degradative RNA exosome. A novel cap-binding protein, NCBP3, was recently proposed to form an alternative CBC together with NCBP1, and to interact with the canonical CBC along with the protein SRRT. The theme of post-transcriptional RNA fate, and how it relates to co-transcriptional ribonucleoprotein assembly, is abundant with complicated, ambiguous, and likely incomplete models. In an effort to clarify the compositions of NCBP1-, 2- and 3-related macromolecular assemblies, we have applied an affinity capture-based interactome screen where the experimental design and data processing have been modified to quantitatively identify interactome differences between targets under a range of experimental conditions. This study generated a comprehensive view of NCBP-protein interactions in the ribonucleoprotein context and demonstrates the potential of our approach to benefit the interpretation of complex biological pathways.
Highlights
All RNAs transcribed by RNA polymerase II (RNAPII) are modified at the 5 -end early during transcription with an N7-methylguanosine (m7G) linked in a 5 -to-5 orientation [1,2]
NCBP2 binds directly to the cap, albeit with relatively low affinity; its capbinding affinity is significantly enhanced by its heterodimerization with NCBP1 [4,5], which further serves as a binding platform for different proteins that influence the progression of RNAs towards productive or destructive fates
CBCA can interact with ZC3H18, which may in turn recruit the nuclear exosome targeting () complex or the poly(A) tail exosome targeting (PAXT) connection, directing bound RNAs to decay via the RNA exosome [10,11]
Summary
All RNAs transcribed by RNA polymerase II (RNAPII) are modified at the 5 -end early during transcription with an N7-methylguanosine (m7G) linked in a 5 -to-5 orientation [1,2]. The resulting m7G-cap structure is bound by the nuclear cap-binding complex (CBC), a heterodimer of NCBP1 (CBP80) and NCBP2 (CBP20) [3]. ARS2 (SRRT, Uniprot gene symbols preferentially used throughout) joins the CBC, forming the CBC-ARS2 (CBCA) complex, which influences the fate of multiple types of RNAs [8,9]. CBCA can interact with ZC3H18, which may in turn recruit the nuclear exosome targeting () complex or the poly(A) tail exosome targeting (PAXT) connection, directing bound RNAs to decay via the RNA exosome [10,11]. On snRNAs and a few independently transcribed snoRNAs, the CBCA complex may interact with PHAX, forming the CBCAP complex which stimulates nuclear export of snRNAs and the movement of snoRNAs to nucleoli [9,12,13,14].
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