RNA Binding Motif Protein 48 Is Required for U12 Splicing and Maize Endosperm Differentiation

Abstract

The last eukaryotic common ancestor had two classes of introns that are still found in most eukaryotic lineages. Common U2type and rare U12-type introns are spliced by the major and minor spliceosomes, respectively. Relatively few splicing factors have been shown to be specific to the minor spliceosome. We found that the maize (Zea mays) RNA binding motif protein 48 (RBM48) is a U12 splicing factor that functions to promote cell differentiation and repress cell proliferation. RBM48 is coselected with the U12 splicing factor, zinc finger CCCH-type, RNA binding motif, and Ser/Arg rich 2/Rough endosperm 3 (RGH3). Protein-protein interactions between RBM48, RGH3, and U2 Auxiliary Factor (U2AF) subunits suggest major and minor spliceosome factors required for intron recognition form complexes with RBM48. Human RBM48 interacts with armadillo repeat containing 7 (ARMC7). Maize RBM48 and ARMC7 have a conserved protein-protein interaction. These data predict that RBM48 is likely to function in U12 splicing throughout eukaryotes and that U12 splicing promotes endosperm cell differentiation in maize.

Androgenic regulation of sexually dimorphic expression of RNA binding motif protein 48 in the developing mouse cortex and hippocampus

“…The results showed signiicant enrichment for terms related exclusively to the chemical reactions and cellular pathways that involve RNA, including RNA processing (GO:0006396), RNA splicing (GO:0008380), gene expression (GO:0010467), RNA metabolic process (GO:0016070), RNA localization (GO:0006403), RNA transport (GO:0050658), RNA stabilization (GO:0043489), and translation (GO:0006412), unsurprisingly suggesting that like many members of the RBD superfamily, RBM48 may control the fate of its bound RNAs by governing a single or multiple aspects of RNA biology, from transcription, splicing and polyadenylation to RNA modiication, transport, localization, translation and turnover. Bai and colleagues (2019) have recently discovered RBM48 to function as a minor spliceosome factor in U12 splicing in plants (corn), and Rbm48 mutations cause aberrant splicing of U12-type introns and the defects that repress endosperm cell diferentiation during development (Bai et al, 2019). Since RBM48 is a highly conserved protein, mouse RBM48 is predicted to also function in U12 splicing.…”

Structure of the activated human minor spliceosome

“…The RNA binding motif (RRM) containing protein RBM48 is essential for splicing of U12-type introns in both plants and animals (47,48). It interacts with the protein armadillo repeat containing 7 (ARMC7) (47)(48)(49).…”

“…The RNA binding motif (RRM) containing protein RBM48 is essential for splicing of U12-type introns in both plants and animals (47,48). It interacts with the protein armadillo repeat containing 7 (ARMC7) (47)(48)(49). RBM48-deficient human cell lines and maize endosperm display aberrant splicing of the U12-type introns, which may lead to developmental defects (47,48).…”

“…It interacts with the protein armadillo repeat containing 7 (ARMC7) (47)(48)(49). RBM48-deficient human cell lines and maize endosperm display aberrant splicing of the U12-type introns, which may lead to developmental defects (47,48). However, the role of RBM48 in U12-dependent splicing remains unknown.…”

Minor Splicing Factors Zrsr1 and Zrsr2 Are Essential for Early Embryo Development and 2-Cell-Like Conversion

“…Mutations within both the protein and snRNA components of the minor spliceosome have been associated with multiple diseases, including developmental disorders [4,[6][7][8][9], neurodegeneration [10], and cancer [11]. Additionally, the minor spliceosome is thought to play an important developmental role in plants [12][13][14], drosophila [15] zebrafish [16], and in the mouse central nervous system [17,18], hypothalamus [19], gametogenesis [9], and early development [20]. Systematic transcriptome and proteome analyses of mouse and human preimplantation embryos have revealed that genes involved in mRNA splicing are over-represented during early preimplantation development [21], before and during zygotic gene activation (ZGA) [22].…”