Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing. |
| Συγγραφείς: |
Seungjae Lee, Sangmi Lee, Desnick, Robert, Makiko Yasuda, Lai, Eric C. |
| Πηγή: |
Science (pre-March 2025); 12/20/2024, Vol. 386 Issue 6728, p1427-1434, 8p, 5 Diagrams |
| Θεματικοί όροι: |
Small interfering RNA, Heme, Biosynthesis, Liver cells |
| Εταιρία/Οντότητα: |
United States. Food & Drug Administration |
| Περίληψη: |
microRNAs (miRNAs) and small interfering RNAs (siRNAs) are 21- to 22-nucleotide RNAs that guide Argonaute-class effectors to targets for repression. In this work, we uncover 5-aminolevulinic acid synthase 1 (ALAS1), the initiating enzyme for heme biosynthesis, as a general repressor of miRNA accumulation. Although heme is known to be a positive cofactor for the nuclear miRNA processing machinery, ALAS1—but not other heme biosynthesis enzymes—limits the assembly and activity of Argonaute complexes under heme-replete conditions. This involves a cytoplasmic role for ALAS1, previously considered inactive outside of mitochondria. Moreover, conditional depletion of ALAS activity from mouse hepatocytes increases miRNAs and enhances siRNA-mediated knockdown. Notably, because ALAS1 is the target of a Food and Drug Administration–approved siRNA drug, agents that suppress ALAS may serve as adjuvants for siRNA therapies. [ABSTRACT FROM AUTHOR] |
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| Βάση Δεδομένων: |
Complementary Index |