Splicing and dicing with a SERRATEd edge.

T he maturation and quality control of mRNA in eukaryotes is a tightly regulated, multistep process that begins on nascent transcripts. A 7-methyl guanosine (7MeG) cap structure is added to the 5 end of pre-mRNA as it emerges from the exit channel of RNA Polymerase II. The multifunctional nuclear cap-binding complex (CBC), consisting of two protein subunits (CBP80 and CBP20), assembles at the pre-mRNA cap early during transcript formation and helps recruit the splicesome machinery to the cap-proximal intron (1, 2). Termination of transcription involves cleavage and polyadenylation at the 3 end, and the mature mRNA is retained in the nucleus or exported to the cytoplasm. In either case, the mRNA undergoes a pioneer round of translation and surveillance by the nonsense-mediated mRNA decay (NMD) pathway to eliminate defective or misspliced transcripts. Although the CBC localizes primarily to the nucleus, it remains associated with mRNAs during export to the cytoplasm and during the pioneer round of translation and mRNA surveillance. After the first round of translation, the CBC is replaced by the eukaryotic initiation complex eIF4F, and the mRNA steadystate translation initiation complex is formed (3). But not all RNA Pol II transcripts are predestined for translation. Primary transcripts for microRNA (pri-miRNA) are retained in the nucleus, where they are processed into 21to 22-nt miRNA that generally function as posttranscriptional regulators of mRNA expression. Although it is known that pri-miRNA transcripts form by RNA Pol II transcription, the extent to which pri-miRNA and pre-mRNA transcripts share common processing components is far from settled. In this issue of PNAS, Laubinger et al. (4) identify an important relationship between mRNA maturation and miRNA primary transcript processing in plants. The CBC was initially identified in human cells through its role in splicing and has since been shown to be important for multiple mRNA functions (1, 5). The plant homolog of the large subunit of the CBC, CBP80, was first isolated in a genetic screen for Arabidopsis thaliana mutants with hypersensitivity to the plant hormone abscisic acid (ABA) and thus was designated ABA HYPERSENSITIVE1 (ABH1). ABH1/CBP80 was shown to interact with an Arabidopsis homolog of the smaller subunit of the CBC, CBP20, and to form a complex that binds the 7MeG cap of mRNA, confirming that the CBC shares biochemical functions in plants, humans, and yeast (6). Although ABH1/CBP80 and CBP20 are not essential for plant viability under controlled or luxurious growth conditions, plants lacking or deficient in these factors display pleiotropic abnormalities, including jagged-edge leaf morphology defects and increased drought tolerance (6–8). Laubinger et al. (4) recognized, as did others (7, 9), that the serrated leaf phenotype of abh1/cbp80 and cbp20 mutant plants was reminiscent of a phenotype observed nearly 40 years earlier in the mutant serrate (10). Convergence of this specific leaf phenotype could mean that the affected genes function in the same biochemical or developmental pathway. Whereas abh1/cbp80 and cbp20 mutants have relatively mild phenotypes, hypomorphic serrate alleles have a variety of severe developmental defects relating to developmental timing, phylotaxy, meristem function, and patterning in leaves and flowers (11–13). serrate-null mutants are embryonic-lethal (14), and, similar to abh1/cbp80 mutants, serrate mutants are hypersensitive to ABA (7). SERRATE encodes a zinc-finger protein (12). Although SERRATE had not been directly implicated in mRNA metabolism, Bezerra et al. (7) presciently suggested that SERRATE and the CBC might function through a common mechanism involving RNA metabolism. More recently, SERRATE was shown to be a critical component of the pri-miRNA processing machinery and to interact and colocalize with other miRNA biogenesis factors (14–17). Until now, the link between SERRATE and the CBC remained elusive. SERRATE is one of several factors involved in miRNA processing. Similar to other RNA Pol II products, primRNA transcripts contain a 7MeG cap structure at the 5 terminus and a 3 poly(A) tail, but they are distinguished from mRNA by their lack of a functional coding sequence and possession of a self-complementary foldback re-