Mammalian mRNA splice-isoform selection is tightly controlled.

Abstract:

:Post-transcriptional RNA processing is an important regulatory control mechanism for determining the phenotype of eukaryotic cells. The processing of a transcribed RNA species into alternative splice isoforms yields products that can perform different functions. Each type of cell in a multi-cellular organism is presumed to actively control the relative quantities of alternative splice isoforms. In this study, the alternatively spliced isoforms of five mRNA transcription units were examined by quantitative reverse transcription-PCR amplification. We show that interindividual variation in splice-isoform selection is very highly constrained when measured in a large population of genetically diverse mice (i.e., full siblings; N = 150). Remarkably, splice-isoform ratios are among the most invariant phenotypes measured in this population and are confirmed in a second, genetically distinct population. In addition, the patterns of splice-isoform selection show tissue-specific and age-related changes. We propose that splice-isoform selection is exceptionally robust to genetic and environmental variability and may provide a control point for cellular homeostasis. As a consequence, splice-isoform ratios may be useful as a practical quantitative measure of the physiological status of cells and tissues.

journal_name

Genetics

journal_title

Genetics

authors

Chisa JL,Burke DT

doi

10.1534/genetics.106.066183

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

1079-87

issue

3

eissn

0016-6731

issn

1943-2631

pii

genetics.106.066183

journal_volume

175

pub_type

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