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| Status |
Public on Jun 25, 2021 |
| Title |
Alternative splicing regulates the physiological adaptation of the mouse hind limb postural and phasic muscles to microgravity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We sought to comprehensively elucidate the transcriptomic underpinnings of microgravity-induced muscle phenotypes in mice by evaluating both differential gene expression (DGE) and changes in alternative splicing (AS) due to extended spaceflight. Total RNA was isolated from the gastrocnemius and quadriceps, postural and phasic muscles of the hind limb, respectively, of 32-week-old female BALB/c mice exposed to microgravity or ground control conditions for nine weeks. RNA sequencing revealed that DGE and AS varied across postural and phasic muscle types with preferential employment of DGE in the gastrocnemius and AS in the quadriceps. Gene ontology analysis indicated that DGE and AS regulate distinct molecular processes. Various non-differentially expressed transcripts encoding musculoskeletal proteins (Tnnt3, Tnnt1, Neb, Ryr1, and Ttn) and muscle-specific RNA binding splicing regulators (Mbnl1 and Rbfox1) were found to have significant changes in AS that altered critical functional domains of their protein products. In striking contrast, microgravity-induced differentially expressed genes were associated with translation/ribosomal function and lipid metabolism. Our work serves as the first comprehensive investigation of coordinate changes in DGE and AS in large limb muscles across spaceflight. We propose that substantial remodeling of pre-mRNA by AS is a major component of transcriptomic adaptation of skeletal muscle to microgravity. The alternatively spliced genes identified here could be targeted by small molecule splicing regulator therapies to address microgravity-induced changes in muscle during spaceflight.
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| Overall design |
Evaluate DGE and AS in hindlimb muscles of mice exposed to microgravity.
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| Contributor(s) |
Mason H, Yuanyuan W |
| Citation(s) |
35642060 |
| Submission date |
Jun 24, 2021 |
| Last update date |
Aug 16, 2022 |
| Contact name |
Yuanyuan Wang |
| E-mail(s) |
wyynju1993@gmail.com
|
| Phone |
3108693302
|
| Organization name |
UCLA
|
| Street address |
3720 Chestnut St, Apt 709
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA741193 |
| SRA |
SRP325481 |
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