Faculty Collaboration Database

Stage-Specific Timing of the microRNA Regulation of lin-28 by the Heterochronic Gene lin-14 in Caenorhabditis elegans. Genetics 2017 Jan;205(1):251-262

Date

11/07/2016

Pubmed ID

27815363

Pubmed Central ID

PMC5223506

DOI

10.1534/genetics.116.195040

Scopus ID

2-s2.0-85008469074 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

In normal development, the order and synchrony of diverse developmental events must be explicitly controlled. In the nematode Caenorhabditis elegans, the timing of larval events is regulated by hierarchy of proteins and microRNAs (miRNAs) known as the heterochronic pathway. These regulators are organized in feedforward and feedback interactions to form a robust mechanism for specifying the timing and execution of cell fates at successive stages. One member of this pathway is the RNA binding protein LIN-28, which promotes pluripotency and cell fate decisions in successive stages. Two genetic circuits control LIN-28 abundance: it is negatively regulated by the miRNA lin-4, and positively regulated by the transcription factor LIN-14 through a mechanism that was previously unknown. In this report, we used animals that lack lin-4 to elucidate LIN-14's activity in this circuit. We demonstrate that three let-7 family miRNAs-miR-48, miR-84, and miR-241-inhibit lin-28 expression. Furthermore, we show genetically that these miRNAs act between lin-14 and lin-28, and that they comprise the pathway by which lin-14 positively regulates lin-28 We also show that the lin-4 family member mir-237, also regulates early cell fates. Finally, we show that the expression of these miRNAs is directly inhibited by lin-14 activity, making them the first known targets of lin-14 that act in the heterochronic pathway.

Author List

Tsialikas J, Romens MA, Abbott A, Moss EG

Author

Allison Abbott PhD Associate Professor in the Biology department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Cell Differentiation
Gene Expression Regulation, Developmental
Larva
MicroRNAs
Nuclear Proteins
RNA-Binding Proteins
Repressor Proteins
Transcription Factors