A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression
Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undiffe...
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doaj-f5c6b76e271d4878b39ec403e48f53d62020-11-24T21:21:03ZengElsevierCell Reports2211-12472015-10-0113226026610.1016/j.celrep.2015.08.086A Single Let-7 MicroRNA Bypasses LIN28-Mediated RepressionRobinson Triboulet0Mehdi Pirouz1Richard I. Gregory2Stem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USAStem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USAStem Cell Program, Boston Children’s Hospital, Boston, MA 02115, USALet-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undifferentiated cells and in cancer. The current model for coordinate let-7 repression involves the LIN28 cold-shock domain (CSD) binding the terminal loop and the two CCHC-type zinc fingers recognizing a GGAG sequence motif in precursor let-7 (pre-let-7) RNAs. Here, we perform a systematic analysis of all let-7 miRNAs and find that a single let-7 family member, human let-7a-3 (and its murine ortholog let-7c-2), escapes LIN28-mediated regulation. Mechanistically, we find that the pre-let-7c-2 loop precludes LIN28A binding and regulation. These findings refine the current model of let-7 regulation by LIN28 proteins and have important implications for understanding the LIN28/let-7 axis in development and disease.http://www.sciencedirect.com/science/article/pii/S2211124715010116 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Robinson Triboulet Mehdi Pirouz Richard I. Gregory |
spellingShingle |
Robinson Triboulet Mehdi Pirouz Richard I. Gregory A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression Cell Reports |
author_facet |
Robinson Triboulet Mehdi Pirouz Richard I. Gregory |
author_sort |
Robinson Triboulet |
title |
A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression |
title_short |
A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression |
title_full |
A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression |
title_fullStr |
A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression |
title_full_unstemmed |
A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression |
title_sort |
single let-7 microrna bypasses lin28-mediated repression |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-10-01 |
description |
Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain 12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28 proteins selectively block let-7 biogenesis in undifferentiated cells and in cancer. The current model for coordinate let-7 repression involves the LIN28 cold-shock domain (CSD) binding the terminal loop and the two CCHC-type zinc fingers recognizing a GGAG sequence motif in precursor let-7 (pre-let-7) RNAs. Here, we perform a systematic analysis of all let-7 miRNAs and find that a single let-7 family member, human let-7a-3 (and its murine ortholog let-7c-2), escapes LIN28-mediated regulation. Mechanistically, we find that the pre-let-7c-2 loop precludes LIN28A binding and regulation. These findings refine the current model of let-7 regulation by LIN28 proteins and have important implications for understanding the LIN28/let-7 axis in development and disease. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715010116 |
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