MBNL1

MBNL1
Identifiers
AliasesMBNL1, EXP, EXP35, EXP40, EXP42, MBNL, muscleblind like splicing regulator 1
External IDsOMIM: 606516; MGI: 1928482; GeneCards: MBNL1
Available structures
PDBOrtholog search: PDBe RCSB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

4154

56758

Ensembl

ENSG00000152601

ENSMUSG00000027763

UniProt

Q9NR56
Q86VM6

Q9JKP5

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 3: 152.24 – 152.47 MbChr 3: 60.47 – 60.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Muscleblind Like Splicing Regulator 1 (MBNL1) is an RNA splicing protein that in humans is encoded by the MBNL1 gene.[5][6][7] It has a well characterized role in Myotonic dystrophy where impaired splicing disrupts muscle development and function.[8] In addition to regulating mRNA maturation of hundreds of genes MBNL1 (along with its paralogs MBNL2 & MBNL3) autoregulate alternative splicing of the MBNL1 pre-mRNA transcript.[9] The founding member of the human MBNL family of proteins was the Drosophila Muscleblind protein (PMID 9334280).

Human MBNL1 is an alternative splicing regulator that harbors dual function as both a repressor and activator for terminal muscle differentiation.[10] The repressive function of Human MBNL1 by sequestering at normal splice sites has been shown to lead to RNA-splicing defects that lead to muscular diseases.[11] The gene can be alternatively spliced into multiple functionally distinct isoforms, some of which linked to be involved in cancer biology.[12]

Human MBNL1 is a 370 amino acid protein[13] composed of four Zinc Finger protein domains of the CCCH type linked in tandem.[10] The MBNL1 protein specifically binds to double stranded CUG RNA expansions.[14] The Zinc Finger domains play a role in both protein:protein contacts as well as RNA:protein contacts when bound to an oligonucleotide.[10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000152601 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027763 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, et al. (October 1997). "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 4 (5): 307–313. doi:10.1093/dnares/4.5.307. PMID 9455477.
  6. ^ Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, et al. (September 2000). "Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy". The EMBO Journal. 19 (17): 4439–4448. doi:10.1093/emboj/19.17.4439. PMC 302046. PMID 10970838.
  7. ^ "Entrez Gene: MBNL1 muscleblind-like (Drosophila)".
  8. ^ Ho TH, Charlet-B N, Poulos MG, Singh G, Swanson MS, Cooper TA (August 2004). "Muscleblind proteins regulate alternative splicing". The EMBO Journal. 23 (15): 3103–3112. doi:10.1038/sj.emboj.7600300. PMC 514918. PMID 15257297.
  9. ^ Konieczny P, Stepniak-Konieczna E, Sobczak K (January 2018). "MBNL expression in autoregulatory feedback loops". RNA Biology. 15 (1): 1–8. doi:10.1080/15476286.2017.1384119. PMC 5786016. PMID 28949831.
  10. ^ a b c Teplova M, Patel DJ (December 2008). "Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1". Nature Structural & Molecular Biology. 15 (12): 1343–1351. doi:10.1038/nsmb.1519. PMC 4689322. PMID 19043415.
  11. ^ Yadava RS, Kim YK, Mandal M, Mahadevan K, Gladman JT, Yu Q, et al. (July 2019). "MBNL1 overexpression is not sufficient to rescue the phenotypes in a mouse model of RNA toxicity". Human Molecular Genetics. 28 (14): 2330–2338. doi:10.1093/hmg/ddz065. PMC 6606845. PMID 30997488.
  12. ^ Tabaglio T, Low DH, Teo WK, Goy PA, Cywoniuk P, Wollmann H, et al. (October 2018). "MBNL1 alternative splicing isoforms play opposing roles in cancer". Life Science Alliance. 1 (5) e201800157. doi:10.26508/lsa.201800157. PMC 6238595. PMID 30456384.
  13. ^ Tchaicheeyan O (2007). Biophysical characterization of the 117 amino acids long N-terminal segment of D-Raf (Isoform A) (Thesis). Iowa State University. doi:10.31274/rtd-180813-16211.
  14. ^ "MBNL1 muscleblind like splicing regulator 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-05.

Further reading

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