Troponin I3 and Troponin I1 precursor messenger RNAs (TNNI3/TNNI1 pre-mRNAs)

Troponin I3 (TNNI3) and Troponin I1 (TNNI1) pre-mRNAs are the precursor messenger RNA transcripts for the cardiac and slow skeletal isoforms of troponin I, respectively. Troponin I is a critical regulatory protein within the sarcomere that inhibits the interaction between actin and myosin in the absence of calcium, thereby facilitating muscle relaxation (UniProt P19429, P19237). In the heart, a developmental transition occurs where the fetal TNNI1 isoform is replaced by the adult TNNI3 isoform; disruptions in this switch or mutations in the TNNI3 gene are major drivers of hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (PubMed 31515307, 29433868). These pre-mRNAs are targeted by emerging RNA-based therapies, particularly antisense oligonucleotides (ASOs), which aim to correct splicing defects or increase the expression of functional protein in haploinsufficient states (Stoke Therapeutics). By manipulating the splicing patterns of these transcripts, such as through the Targeted Augmentation of Nuclear Gene Output (TANGO) approach, researchers aim to restore sarcomere function and prevent the progression of cardiac remodeling and heart failure.

Other names

Cardiac troponin I pre-mRNASlow skeletal troponin I pre-mRNATNNI3 transcriptTNNI1 transcriptcTnI/ssTnI pre-mRNATroponin I3 (TNNI3) pre-mRNATroponin I1 (TNNI1) pre-mRNA

Modulation of pre-mRNA splicing to increase productive mRNA levels, skip exons containing pathogenic mutations, or facilitate isoform switching.