Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.

Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene expression, mainly at mRNA post-transcriptional level. Functional maturation of most miRNAs requires processing of the primary transcript by Dicer, an RNaseIII-type enzyme. To date, the importance of miRNA function for normal organogen...

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Autores principales:	Wendy Rodriguez, Ling Jin, Véronique Janssens, Christophe Pierreux, Anne-Christine Hick, Eneko Urizar, Sabine Costagliola
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cdfea6e5f3a948cd8dd0e8f9dad0cedf
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spelling	oai:doaj.org-article:cdfea6e5f3a948cd8dd0e8f9dad0cedf2021-11-18T07:30:50ZDeletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.1932-620310.1371/journal.pone.0029929https://doaj.org/article/cdfea6e5f3a948cd8dd0e8f9dad0cedf2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22242190/?tool=EBIhttps://doaj.org/toc/1932-6203Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene expression, mainly at mRNA post-transcriptional level. Functional maturation of most miRNAs requires processing of the primary transcript by Dicer, an RNaseIII-type enzyme. To date, the importance of miRNA function for normal organogenesis has been demonstrated in several mouse models of tissue-specific Dicer inactivation. However, the role of miRNAs in thyroid development has not yet been addressed. For the present study, we generated mouse models in which Dicer expression has been inactivated at two different stages of thyroid development in thyroid follicular cells. Regardless of the time of Dicer invalidation, the early stages of thyroid organogenesis, preceding folliculogenesis, were unaffected by the loss of small RNAs, with a bilobate gland in place. Nevertheless, Dicer mutant mice were severely hypothyroid and died soon after weaning unless they were substituted with T4. A conspicuous follicular disorganization was observed in Dicer mutant thyroids together with a strong down regulation of Nis expression. With increasing age, the thyroid tissue showed characteristics of neoplastic alterations as suggested by a marked proliferation of follicular cells and an ongoing de-differentiation in the center of the thyroid gland, with a loss of Pax8, FoxE1, Nis and Tpo expression. Together, our data show that loss of miRNA maturation due to Dicer inactivation severely disturbs functional thyroid differentiation. This suggests that miRNAs are mandatory to fine-tune the expression of thyroid specific genes and to maintain thyroid tissue homeostasis.Wendy RodriguezLing JinVéronique JanssensChristophe PierreuxAnne-Christine HickEneko UrizarSabine CostagliolaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29929 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wendy Rodriguez Ling Jin Véronique Janssens Christophe Pierreux Anne-Christine Hick Eneko Urizar Sabine Costagliola Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
description	Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene expression, mainly at mRNA post-transcriptional level. Functional maturation of most miRNAs requires processing of the primary transcript by Dicer, an RNaseIII-type enzyme. To date, the importance of miRNA function for normal organogenesis has been demonstrated in several mouse models of tissue-specific Dicer inactivation. However, the role of miRNAs in thyroid development has not yet been addressed. For the present study, we generated mouse models in which Dicer expression has been inactivated at two different stages of thyroid development in thyroid follicular cells. Regardless of the time of Dicer invalidation, the early stages of thyroid organogenesis, preceding folliculogenesis, were unaffected by the loss of small RNAs, with a bilobate gland in place. Nevertheless, Dicer mutant mice were severely hypothyroid and died soon after weaning unless they were substituted with T4. A conspicuous follicular disorganization was observed in Dicer mutant thyroids together with a strong down regulation of Nis expression. With increasing age, the thyroid tissue showed characteristics of neoplastic alterations as suggested by a marked proliferation of follicular cells and an ongoing de-differentiation in the center of the thyroid gland, with a loss of Pax8, FoxE1, Nis and Tpo expression. Together, our data show that loss of miRNA maturation due to Dicer inactivation severely disturbs functional thyroid differentiation. This suggests that miRNAs are mandatory to fine-tune the expression of thyroid specific genes and to maintain thyroid tissue homeostasis.
format	article
author	Wendy Rodriguez Ling Jin Véronique Janssens Christophe Pierreux Anne-Christine Hick Eneko Urizar Sabine Costagliola
author_facet	Wendy Rodriguez Ling Jin Véronique Janssens Christophe Pierreux Anne-Christine Hick Eneko Urizar Sabine Costagliola
author_sort	Wendy Rodriguez
title	Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
title_short	Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
title_full	Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
title_fullStr	Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
title_full_unstemmed	Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
title_sort	deletion of the rnaseiii enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cdfea6e5f3a948cd8dd0e8f9dad0cedf
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Deletion of the RNaseIII enzyme dicer in thyroid follicular cells causes hypothyroidism with signs of neoplastic alterations.

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