Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis
The terminal nucleotidyltransferases TUT4 and TUT7 (TUT4/7) regulate miRNA and mRNA stability by 3′ end uridylation. In humans, TUT4/7 polyuridylates both mRNA and pre-miRNA, leading to degradation by the U-specific exonuclease DIS3L2. We investigate the role of uridylation-dependent decay in mainta...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/23/3742 |
| _version_ | 1797463494543540224 |
|---|---|
| author | Pengcheng Zhang Mallory I. Frederick Ilka U. Heinemann |
| author_facet | Pengcheng Zhang Mallory I. Frederick Ilka U. Heinemann |
| author_sort | Pengcheng Zhang |
| collection | DOAJ |
| description | The terminal nucleotidyltransferases TUT4 and TUT7 (TUT4/7) regulate miRNA and mRNA stability by 3′ end uridylation. In humans, TUT4/7 polyuridylates both mRNA and pre-miRNA, leading to degradation by the U-specific exonuclease DIS3L2. We investigate the role of uridylation-dependent decay in maintaining the transcriptome by transcriptionally profiling TUT4/7 deleted cells. We found that while the disruption of TUT4/7 expression increases the abundance of a variety of miRNAs, the let-7 family of miRNAs is the most impacted. Eight let-7 family miRNAs were increased in abundance in TUT4/7 deleted cells, and many let-7 mRNA targets are decreased in abundance. The mRNAs with increased abundance in the deletion strain are potential direct targets of TUT4/7, with transcripts coding for proteins involved in cellular stress response, rRNA processing, ribonucleoprotein complex biogenesis, cell–cell signaling, and regulation of metabolic processes most affected in the TUT4/7 knockout cells. We found that TUT4/7 indirectly control oncogenic signaling via the miRNA let-7a, which regulates AKT phosphorylation status. Finally, we find that, similar to fission yeast, the disruption of uridylation-dependent decay leads to major rearrangements of the transcriptome and reduces cell proliferation and adhesion. |
| first_indexed | 2024-03-09T17:51:30Z |
| format | Article |
| id | doaj.art-962780eb41e44978a316190febcd8e41 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:30Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-962780eb41e44978a316190febcd8e412023-11-24T10:42:59ZengMDPI AGCells2073-44092022-11-011123374210.3390/cells11233742Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA HomeostasisPengcheng Zhang0Mallory I. Frederick1Ilka U. Heinemann2Department of Biochemistry, University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, CanadaDepartment of Biochemistry, University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, CanadaDepartment of Biochemistry, University of Western Ontario, 1151 Richmond Street, London, ON N6A 5C1, CanadaThe terminal nucleotidyltransferases TUT4 and TUT7 (TUT4/7) regulate miRNA and mRNA stability by 3′ end uridylation. In humans, TUT4/7 polyuridylates both mRNA and pre-miRNA, leading to degradation by the U-specific exonuclease DIS3L2. We investigate the role of uridylation-dependent decay in maintaining the transcriptome by transcriptionally profiling TUT4/7 deleted cells. We found that while the disruption of TUT4/7 expression increases the abundance of a variety of miRNAs, the let-7 family of miRNAs is the most impacted. Eight let-7 family miRNAs were increased in abundance in TUT4/7 deleted cells, and many let-7 mRNA targets are decreased in abundance. The mRNAs with increased abundance in the deletion strain are potential direct targets of TUT4/7, with transcripts coding for proteins involved in cellular stress response, rRNA processing, ribonucleoprotein complex biogenesis, cell–cell signaling, and regulation of metabolic processes most affected in the TUT4/7 knockout cells. We found that TUT4/7 indirectly control oncogenic signaling via the miRNA let-7a, which regulates AKT phosphorylation status. Finally, we find that, similar to fission yeast, the disruption of uridylation-dependent decay leads to major rearrangements of the transcriptome and reduces cell proliferation and adhesion.https://www.mdpi.com/2073-4409/11/23/3742RNA degradationuridylation dependent decaymicroRNA homeostasistranscriptomemiRNA/mRNA networkoncogenic signaling |
| spellingShingle | Pengcheng Zhang Mallory I. Frederick Ilka U. Heinemann Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis Cells RNA degradation uridylation dependent decay microRNA homeostasis transcriptome miRNA/mRNA network oncogenic signaling |
| title | Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis |
| title_full | Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis |
| title_fullStr | Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis |
| title_full_unstemmed | Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis |
| title_short | Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis |
| title_sort | terminal uridylyltransferases tut4 7 regulate microrna and mrna homeostasis |
| topic | RNA degradation uridylation dependent decay microRNA homeostasis transcriptome miRNA/mRNA network oncogenic signaling |
| url | https://www.mdpi.com/2073-4409/11/23/3742 |
| work_keys_str_mv | AT pengchengzhang terminaluridylyltransferasestut47regulatemicrornaandmrnahomeostasis AT malloryifrederick terminaluridylyltransferasestut47regulatemicrornaandmrnahomeostasis AT ilkauheinemann terminaluridylyltransferasestut47regulatemicrornaandmrnahomeostasis |