Weight and nutrition affect pre-mRNA splicing of a muscle gene associated with performance, energetics and life history

Abstract

SUMMARYA fundamental feature of gene expression in multicellular organisms is the production of distinct transcripts from single genes by alternative splicing (AS), which amplifies protein and functional diversity. In spite of the likely consequences for organismal biology, little is known about how AS varies among individuals or responds to body condition, environmental variation or extracellular signals in general. Here we show that evolutionarily conserved AS of troponin-t in flight muscle of adult moths responds in a quantitative fashion to experimental manipulation of larval nutrition and adult body weight. Troponin-t (Tnt) isoform composition is known to affect muscle force and power output in other animals, and is shown here to be associated with the thorax mass-specific rate of energy consumption during flight. Loading of adults with external weights for 5 days caused an AS response nearly identical to equal increases in actual body weight. In addition, there were effects of larval feeding history on adult Tnt isoform composition that were independent of body weight, with moths from poorer larval feeding regimes producing isoform profiles associated with reduced muscle performance and energy consumption rate. Thus, Tnt isoform composition in striated muscle is responsive to both weight-sensing and nutrition-sensing mechanisms, with consequent effects on function. In freeliving butterflies, Tnt isoform composition was also associated with activity level and very strongly with the rate of egg production. Overall, these results show that AS of a muscle gene responds in a quantitative fashion to whole-organism variables, which apparently serves to coordinate muscle strength and energy expenditure with body condition and life history.

A long life in the fast lane: positive association between peak metabolic rate and lifespan in a butterfly

“…A clear peak and subsequent fatigue is routinely seen during measurements of butterfly flight metabolic rate, suggesting that a true metabolic maximum is reached. Also, adding lead weights to the thorax did not increase peak flight metabolic rate in a moth measured using the same technique as in our experiments (Marden et al, 2008). Because peak metabolic rate may be more directly linked with fitness than RMR, we hope to see more work focused on metabolic capacity and lifespan.…”

“…An initially high RMR in newly eclosed individuals may result from a number of processes that take place in a maturing individual, such as egg development in females (Clifford and Woodring, 1986) and preparation of spermatophore production in males. Similarly, the flight muscles of young insects undergo maturation as exemplified by changes in muscle troponin T composition (Marden et al, 2008;Schippers et al, 2010). As the individual grows older, investment in these energy-consuming processes decreases.…”

Differential Expression of Glycerol-3-Phosphate Dehydrogenase Isoforms in Flight Muscles of the Chagas Disease Vector Triatoma infestans (Hemiptera, Reduviidae)

“…In this regard, Marden and others showed that evolutionarily conserved alternative splicing of troponin-t in flight muscle of adult moths responds in a quantitative fashion to experimental manipulation of larval nutrition and adult body weight. 31 Overall, these results showed that alternative splicing of a gene expressed in muscle responds in a quantitative fashion to whole-organism variables, which apparently serves to coordinate muscle strength and energy expenditure with body condition and life history. Consistent with these findings, our results support the hypothesis that isoform expression responds to organism conditions to produce different isoform profiles that are associated with energetic and life-history traits.…”

Body weight-dependent troponin T alternative splicing is evolutionarily conserved from insects to mammals and is partially impaired in skeletal muscle of obese rats

“…A recent study of insect flight muscles demonstrated that there is precise quantitative variation in the relative abundance of alternatively spliced troponin T mRNA transcripts and protein isoforms in response to experimental manipulation of body weight and nutritional state (Marden et al, 2008). Here, we used rats to test the hypothesis that in a mammalian load-bearing (gastrocnemius) muscle, quantitative alternative pre-mRNA splicing of Tnnt3 is similarly regulated in response to natural and experimentally imposed variation in body weight.…”