MBNL1
Description
The MBNL1 (muscleblind like splicing regulator 1) is a protein-coding gene located on chromosome 3.
Muscleblind Like Splicing Regulator 1 (MBNL1) is a protein that plays a crucial role in RNA splicing, particularly in humans. It is encoded by the MBNL1 gene and is known for its involvement in Myotonic dystrophy, a disorder where impaired splicing disrupts muscle development and function. MBNL1, along with its related proteins MBNL2 and MBNL3, regulates the maturation of hundreds of genes. Interestingly, MBNL1 also self-regulates its own alternative splicing. The MBNL family originated from the Drosophila Muscleblind protein. Human MBNL1 is a versatile splicing regulator, acting as both a repressor and an activator during terminal muscle differentiation. Its repressive function involves binding to normal splice sites, which can lead to RNA splicing defects and muscular diseases. MBNL1 can be alternatively spliced into multiple functionally distinct isoforms, some of which are linked to cancer biology. MBNL1 is a 370 amino acid protein with four Zinc Finger protein domains of the CCCH type arranged in tandem. The protein specifically binds to double-stranded CUG RNA expansions. These Zinc Finger domains are crucial for both protein-protein interactions and RNA-protein interactions when bound to oligonucleotides.
MBNL1 regulates alternative splicing of pre-mRNA, acting as both an activator and repressor of splicing. It inhibits the inclusion of exon 5 in cardiac troponin-T (TNNT2) pre-mRNA but promotes the inclusion of exon 11 in insulin receptor (IR) pre-mRNA, particularly in muscle. MBNL1 counteracts the splicing activity of CELF proteins and influences TNNT2 exon 5 skipping through competition with U2AF2. It interferes with the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA and binds to a stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. MBNL1 recognizes the 5'-YGCU(U/G)Y-3' consensus sequence and binds to IR RNA. It binds to expanded CUG repeat RNA, which forms a hairpin structure containing GC base pairs and bulged, unpaired U residues. In collaboration with RBPMS and RBFOX2, MBNL1 activates alternative splicing events in vascular smooth muscle cells. It also regulates the alternative splicing of NCOR2.
MBNL1 is also known as EXP, MBNL.
