# ALTERNATIVE SPLICING OF CONTRACTILE PROTEIN GENES

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 1989 · $129,231

## Abstract

Alkali myosin light chain (MLC1/3), Alpha-tropomyosin (Alpha-TM) and
troponin T (TNT) are three genes expressed in sarcomeric muscles.  Each one
of these genes generates multiple mRNAs, each coding for a different
protein isoform, by a process of alternative splicing.  In the case of the
MLC1/3 gene, two alternatively spliced mRNAs (coding for MLC1 and MLC3,
respectively) are produced from two different and overlapping
transcriptional units whose promoters are located 10kb apart but terminate
at the same poly A addition site.  The Alpha-TM gene produces a minimum of
three difference mRNAs that are alternatively spliced at both the 5' and 3'
ends.  It is possible that the conformation of primary transcript with
differences at either the 5' end, the 3' end or both, is responsible for
the splice site selection that determines the alternative splicing
pathways.  Troponin T on the other hand, produces a minimum of 10 different
mRNAs, with the potential to generate up to 64, with identical 5' and 3'
ends by alternative splicing of internal exons from a unique primary
transcript.  Since the expression of these different TNT mRNA isoforms is
developmental and tissue-specific, it is likely that cell-specific
diffusable factors are involved in the regulation of the splicing pathways
of this single primary transcript.

The specific aims of this proposal are three fold:  1) To determine the
relative role of the structure of primary transcripts and putative
trans-acting factors in the production of regulated alternative splicing
pattern in muscle cells.  2) Using specific gene constructs, to determine
the cell and/or gene-specificity of the trans-acting factors involved in
alternative splicing by studying their expression in muscle and non-muscle
cells.  3) To initiate the characterization of these factors using in vitro
and in vivo splicing systems.

## Key facts

- **NIH application ID:** 3157782
- **Project number:** 5R01AR036865-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **SAM.gov UEI:** Z1L9F1MM1RY3
- **Principal Investigator:** Bernardo Nadal Ginard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $129,231
- **Award type:** 5
- **Project period:** 1986-01-01 → 1990-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157782

## Citation

> US National Institutes of Health, RePORTER application 3157782, ALTERNATIVE SPLICING OF CONTRACTILE PROTEIN GENES (5R01AR036865-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157782. Licensed CC0.

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