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| Status |
Public on May 14, 2024 |
| Title |
Study of the tRNA-derived fragment expression profile in mouse pancreatic islets of pre-diabetic obese db/db mice |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We analyzed hundreds of these fragments in the pancreatic islets of db/db mice and compared them to heterozygous control db/+ mice. At 16 weeks of age, db/db mice exhibit obesity, insulin resistance, and glucose intolerance. In our analysis, we identified 3858 tRFs in the islets of db/db mice, among which 342 exhibited significant changes (≥ 2 fold; adjusted p value ≤ 0.05) compared to controls. Of these, 199 tRFs showed increased levels, while 170 tRFs showed decreased levels in the pre-diabetic mice. Notably, a striking majority (147 out of 170) of the tRFs with reduced abundance in the islets of db/db mice were derived from the cleavage of tRNAs encoded by the mitochondrial genome. Our findings reveal a significant reshaping of mitochondrial tRFs in pre-diabetic conditions, coinciding with a well-established mitochondrial metabolic defect under these conditions. Specifically, we demonstrated that a fragment (named mt-tRF-LeuTAA) resulting from the cleavage of mt-tRNA-LeuTAA, encoded by the mitochondrial genome and found to be reduced in the islets of db/db mice, acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells.
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| Overall design |
In order to characterize the expression profile of tRFs (tRNA-derived fragments) in a pre-diabetic context, we isolated total RNA from pancreatic islets of three db/db mice and compared it to that of three heterozygous controls (db/+ mice).
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| Contributor(s) |
Jacovetti C, Donnelly C, Menoud V, Suleiman M, Cosentino C, Sobel J, Wu K, Bouzakri K, Marchetti P, Guay C, Kayser B, Regazzi R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 01, 2023 |
| Last update date |
May 14, 2024 |
| Contact name |
Cecile Jacovetti |
| E-mail(s) |
Cecile.Jacovetti@unil.ch
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| Phone |
+41216925281
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| Organization name |
University of Lausanne
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| Department |
Fundamental Neurosciences
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| Street address |
Rue du Bugnon 9
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| City |
Lausanne |
| ZIP/Postal code |
1005 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| GSM7673195 |
pancreatic mouse islets, het control db/+_1, 16-week-old |
| GSM7673196 |
pancreatic mouse islets, het control db/+_2, 16-week-old |
| GSM7673197 |
pancreatic mouse islets, het control db/+_3, 16-week-old |
| GSM7673198 |
pancreatic mouse islets, pre-diabetic db/db_1, 16-week-old |
| GSM7673199 |
pancreatic mouse islets, pre-diabetic db/db_2, 16-week-old |
| GSM7673200 |
pancreatic mouse islets, pre-diabetic db/db_3, 16-week-old |
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| Relations |
| BioProject |
PRJNA1000965 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239786_tRFs_detected_in_db_db_mouse_islets_versus_controls.xlsx |
9.9 Mb |
(ftp)(http) |
XLSX |
| GSE239786_tRFs_up_and_down_in_db_db_mouse_islets_versus_controls.xlsx |
83.8 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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