The microRNA-processing enzyme Dicer is essential for thyroid function

• Published in: PloS one Vol. 6; no. 11; p. e27648
• Main Authors: Frezzetti, Daniela, Reale, Carla, Calì, Gaetano, Nitsch, Lucio, Fagman, Henrik, Nilsson, Ola, Scarfò, Marzia, De Vita, Gabriella, Di Lauro, Roberto
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.11.2011; Public Library of Science (PLoS)
• Subjects: Aberration; Animals; Animals, Newborn; Biology; Biomarkers - metabolism; Biosynthesis; Body weight; Cancer; Cancer and Oncology; Cancer och onkologi; Cell Adhesion Molecules - metabolism; Cell and Molecular Biology; Cell Differentiation; Cell- och molekylärbiologi; Congenital diseases; Deregulation; Differentiation; Embryo, Mammalian - enzymology; Embryo, Mammalian - pathology; Endocrinology; Enzyme Activation; Enzymes; Fluorescent Antibody Technique; Gene expression; Genes; Genetic aspects; Hormones; Humans; Hypothyroidism; Hypothyroidism - enzymology; Hypothyroidism - pathology; Life span; Machinery and equipment; Medicine; Metastasis; Mice; Mice, Knockout; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Morphogenesis; Oxyphil Cells - metabolism; Oxyphil Cells - pathology; Post-transcription; Ribonuclease; Ribonuclease III; Ribonuclease III - metabolism; Ribonucleic acid; RNA; RNA Processing, Post-Transcriptional; Stem cells; Thyroid; Thyroid gland; Thyroid Gland - enzymology; Thyroid Gland - growth & development; Thyroid Gland - pathology; Thyroid hormones; Transcription (Genetics); Transcription factors; Weight reduction; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0027648

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.