HnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function

Junqiang Ye, Nadine Beetz, Sean O'Keeffe, Juan Carlos Tapia, Lindsey Macpherson, Weisheng V. Chen, Rhonda Bassel-Duby, Eric N. Olson, Tom Maniatis

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


We report that mice lacking the heterogeneous nuclear ribonucleoprotein U (hnRNP U) in the heart develop lethal dilated cardiomyopathy and display numerous defects in cardiac pre-mRNA splicing. Mutant hearts have disorganized cardiomyocytes, impaired contractility, and abnormal excitation-contraction coupling activities. RNA-seq analyses of Hnrnpu mutant hearts revealed extensive defects in alternative splicing of pre-mRNAs encoding proteins known to be critical for normal heart development and function, including Titin and calcium/calmodulin-dependent protein kinase II delta (Camk2d). Loss of hnRNP U expression in cardiomyocytes also leads to aberrant splicing of the pre-mRNA encoding the excitation-contraction coupling component Junctin. We found that the protein product of an alternatively spliced Junctin isoform is N-glycosylated at a specific asparagine site that is required for interactions with specific protein partners. Our findings provide conclusive evidence for the essential role of hnRNP U in heart development and function and in the regulation of alternative splicing.

Original languageEnglish (US)
Pages (from-to)E3020-E3029
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Jun 9 2015


  • Alternative splicing
  • Dilated cardiomyopathy
  • Heart development
  • N-glycosylation
  • RNA-seq

ASJC Scopus subject areas

  • General


Dive into the research topics of 'HnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function'. Together they form a unique fingerprint.

Cite this