MBNL1
MBNL1 (muscleblind like splicing regulator 1) is a C3H-type zinc finger RNA-binding protein that regulates alternative splicing of pre-mRNAs. It is also known as MBNL, EXP, EXP35, EXP40, EXP42 and KIAA0428. Browse Assay Genie's current range of MBNL1 research reagents below, or read on for the biology behind the target.
MBNL1 mediates regulation of pre-mRNA alternative splicing. Depending on the pre-mRNA target, it acts either as an activator or as a repressor of splicing. In muscle it inhibits inclusion of the cardiac troponin-T (TNNT2) exon, yet promotes inclusion of the insulin receptor (IR) exon. It also antagonises the alternative splicing activity pattern of CELF proteins.
At the mechanistic level, MBNL1 regulates TNNT2 exon 5 skipping by competing with U2AF2, and it inhibits formation of the spliceosome A complex on intron 4 of the TNNT2 pre-mRNA. It binds the stem-loop structure within the polypyrimidine tract of that intron, recognises the 5'-YGCU(U/G)Y-3' consensus sequence and binds IR RNA. Together with the RNA-binding proteins RBPMS and RBFOX2, it activates alternative splicing events in vascular smooth muscle cells, and it regulates alternative splicing of NCOR2.
The MBNL1 gene encodes a member of the muscleblind protein family, first described in Drosophila melanogaster, and the protein is found in the nucleus, cytoplasm and cytoplasmic granules. Muscleblind proteins bind specifically to expanded CUG repeat RNA, which folds into a hairpin containing GC base pairs and bulged, unpaired U residues, but not to normal-size CUG repeats. This property may contribute to the pathophysiology of myotonic dystrophy. Mice lacking the gene show muscle abnormalities and cataracts. Several alternatively spliced transcript variants exist, and the isoforms are thought to differ in binding specificity or splicing activity. Earlier names include muscleblind (Drosophila)-like.
MBNL1 acts as an activator or repressor of splicing on specific pre-mRNA targets, making it a model for studying exon inclusion and skipping.
Binding of MBNL1 to expanded CUG repeat RNA, but not normal-size repeats, may underlie the pathophysiology of myotonic dystrophy.
MBNL1 controls TNNT2 and insulin receptor exon choice in muscle, and mouse knockouts show muscle abnormalities.
MBNL1 opposes CELF proteins and cooperates with RBPMS and RBFOX2 in vascular smooth muscle splicing programmes.
MBNL1 regulates alternative splicing of pre-mRNAs, acting as an activator or repressor depending on the target. It inhibits TNNT2 exon inclusion, promotes insulin receptor exon inclusion in muscle, and antagonises CELF proteins. It binds RNA containing the 5'-YGCU(U/G)Y-3' consensus sequence.
MBNL1 is also called MBNL, EXP, EXP35, EXP40, EXP42 and KIAA0428, and its protein name is muscleblind-like protein 1. Earlier names include muscleblind (Drosophila)-like. Several alternatively spliced transcript variants are described, and the isoforms are thought to differ in binding specificity or splicing activity.
MBNL1 binds expanded CUG repeat RNA and may therefore contribute to the pathophysiology of myotonic dystrophy. Orthologues exist in mouse and rat, both named Mbnl1. Mice lacking the gene show muscle abnormalities and cataracts. Check the datasheet of any product for its validated reactivity.
Other muscleblind family members and splicing-regulator targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NR56; product specifications from Assay Genie datasheets.