Expression pattern of muscleblind-like proteins differs in differentiating myoblasts

Lee, Kyung Soon; Squillace, Rachel M.; Wang, Edith H.

doi:10.1016/j.bbrc.2007.06.165

Cited by 19 publications

(19 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MBNL paralogs differ considerably in terms of function and expression level during embryonic and postnatal development ( 12–18 ). While MBNL1 is the major MBNL family member in adult skeletal muscles and governs myoblast differentiation, MBNL3 is mostly present at early stages of development as well as in the adult placenta, spleen and lung ( 15 , 19 ). MBNL1 is partially compensated by upregulation of MBNL2 but not by MBNL3 ( 7 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

MBNL splicing activity depends on RNA binding site structural context

Taylor

Sznajder

Cywoniuk

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

Muscleblind-like (MBNL) proteins are conserved RNA-binding factors involved in alternative splicing (AS) regulation during development. While AS is controlled by distribution of MBNL paralogs and isoforms, the affinity of these proteins for specific RNA-binding regions and their location within transcripts, it is currently unclear how RNA structure impacts MBNL-mediated AS regulation. Here, we defined the RNA structural determinants affecting MBNL-dependent AS activity using both cellular and biochemical assays. While enhanced inclusion of MBNL-regulated alternative exons is controlled by the arrangement and number of MBNL binding sites within unstructured RNA, when these sites are embedded in a RNA hairpin MBNL binds preferentially to one side of stem region. Surprisingly, binding of MBNL proteins to RNA targets did not entirely correlate with AS efficiency. Moreover, comparison of MBNL proteins revealed structure-dependent competitive behavior between the paralogs. Our results showed that the structure of targeted RNAs is a prevalent component of the mechanism of alternative splicing regulation by MBNLs.

show abstract

Section: Introductionmentioning

confidence: 99%

MBNL splicing activity depends on RNA binding site structural context

Taylor

Sznajder

Cywoniuk

et al. 2018

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Studies examining MBNL transcript levels have revealed distinct patterns of expression for MBNL1, MBNL2, and MBNL3 during development and in the adult mouse. (4)(5)(6) These findings suggest that MBNL1, MBNL2, and MBNL3 may display distinct cellular functions in different tissues. Knowledge about protein expression patterns in the adult animal can provide insights into a protein's physiological function.…”

Section: Introductionmentioning

confidence: 86%

“…(8) The expression level of MBNL1 remains unchanged during muscle differentiation. (6,9) However, MBNL1 rapidly redistributes from the nucleus to the cytoplasm in cultures of primary human myoblasts executing the muscle differentiation program. (9) These results prompted us to examine the distribution and localization of MBNL3 in myogenic cells.…”

Section: Lee Et Almentioning

confidence: 99%

“…(8,19) Monoclonal and polyclonal antibodies against MBNL1 revealed that MBNL1 expression levels do not decrease during muscle differentiation, a pattern that has been observed for MBNL2 and MBNL3. (6,9) We have generated monoclonal antibodies against mouse MBNL3 by immunizing animals with the full-length mouse protein and found that MBNL3 is expressed in proliferating muscle precursor cells and not in terminally differentiated myotubes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Monoclonal Antibodies Against Muscleblind-like 3, a Protein with Punctate Nuclear Localization

et al. 2011

Self Cite

View full text Add to dashboard Cite

Muscleblind-like 3 (MBNL3) belongs to a family of RNA binding proteins that regulate alternative splicing. We have generated a set of monoclonal antibodies (MAbs) against mouse MBNL3, three of which do not cross-react with the other muscleblind-like (MBNL) proteins, MBNL1 and MBNL2. Epitope mapping revealed that MAbs P1C7, P1E7, SP1C2, and P2E6 recognize distinct, non-overlapping segments of the MBNL3 polypeptide sequence. Immunohistochemical staining of proliferating muscle precursor cells localized MBNL3 to the nucleus in a punctate pattern, characteristic of subcellular structures in the nucleus enriched in pre-messenger RNA splicing factors. Although MBNL3 did not co-localize with SC35 and PSP1 (widely used markers of splicing speckles and paraspeckles), the punctate localization pattern of MBNL3 within interchromatin regions of the nucleus is highly predictive of proteins involved in pre-mRNA processing. Monoclonal antibodies specific for mouse MBNL3 will facilitate further investigation of the expression pattern and unique functions of this splicing factor during development and in different adult mouse tissues.

show abstract

“…In mammals, MBNL1 is expressed mainly in adult skeletal muscle, heart, brain, intestine, kidney, liver, lung, and placenta; a similar expression pattern is reported for MBNL2, although the level of expression in skeletal muscle is not as high as MBNL1. By contrast, MBNL3 expression occurs mainly in the placenta (Fardaei et al , 2002; Kanadia et al , 2003 b ; Lee, Squillace & Wang, 2007; Miller et al , 2000). In addition to these studies with adult tissue samples, experiments with human and mouse myoblasts have also confirmed temporal changes in the pattern of expression of MBNL proteins throughout muscle development, which are species‐specific (Holt et al , 2009; Miller et al , 2000).…”

Section: Expression Of Muscleblind In Terminally Differentiating mentioning

confidence: 96%

Alternative splicing regulation by Muscleblind proteins: from development to disease

et al. 2011

View full text Add to dashboard Cite

Regulated use of exons in pre-mRNAs, a process known as alternative splicing, strongly contributes to proteome diversity. Alternative splicing is finely regulated by factors that bind specific sequences within the precursor mRNAs. Members of the Muscleblind (Mbl) family of splicing factors control critical exon use changes during the development of specific tissues, particularly heart and skeletal muscle. Muscleblind homologs are only found in metazoans from Nematoda to mammals. Splicing targets and recognition mechanisms are also conserved through evolution. In this recognition, Muscleblind CCCH-type zinc finger domains bind to intronic motifs in pre-mRNA targets in which the protein can either activate or repress splicing of nearby exons, depending on the localization of the binding motifs relative to the regulated alternative exon. In humans, the Muscleblind-like 1 (MBNL1) proteins play a critical role in hereditary diseases caused by microsatellite expansions, particularly myotonic dystrophy type 1 (DM1), in which depletion of MBNL1 activity through sequestration explains most misregulated alternative splicing events, at least in murine models. Because of the involvement of these proteins in human diseases, further understanding of the molecular mechanisms by which MBNL1 regulates splicing will help design therapies to revert pathological splicing alterations. Here we summarize the most relevant findings on this family of proteins in recent years, focusing on recently described functional motifs, transcriptional regulation of Muscleblind, regulatory activity on splicing, and involvement in human diseases.

show abstract

Expression pattern of muscleblind-like proteins differs in differentiating myoblasts

Cited by 19 publications

References 23 publications

MBNL splicing activity depends on RNA binding site structural context

MBNL splicing activity depends on RNA binding site structural context

Monoclonal Antibodies Against Muscleblind-like 3, a Protein with Punctate Nuclear Localization

Alternative splicing regulation by Muscleblind proteins: from development to disease

Contact Info

Product

Resources

About