MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode

Abstract

Animal microRNAs (miRNAs) are gene regulatory factors that prevent the expression of specific messenger RNA targets by binding to their 3' untranslated region. The Caenorhabditis elegans lsy-6 miRNA (for lateral symmetry defective) is required for the left/right asymmetric expression of guanyl cyclase (gcy) genes in two chemosensory neurons termed ASE left (ASEL) and ASE right (ASER). The asymmetric expression of these putative chemoreceptors in turn correlates with the functional lateralization of the ASE neurons. Here we find that a mutation in the die-1 zinc-finger transcription factor disrupts both the chemosensory laterality and left/right asymmetric expression of chemoreceptor genes in the ASE neurons. die-1 controls chemosensory laterality by activating the expression of lsy-6 specifically in ASEL, but not in ASER, where die-1 expression is downregulated through two sites in its 3' untranslated region. These two sites are complementary to mir-273, a previously uncharacterized miRNA, whose expression is strongly biased towards ASER. Forced bilateral expression of mir-273 in ASEL and ASER causes a loss of asymmetric die-1 expression and ASE laterality. Thus, an inverse distribution of two sequentially acting miRNAs in two bilaterally symmetric neurons controls laterality of the nematode chemosensory system.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Ever since their discovery, the number of newly identified human miRNAs has been increasing constantly, and more than 2500 known sequences have been identified thus far [16]. This corresponds to approximately 1-4% of all expressed genes in humans, and thus, miRNAs are currently considered as one of the largest classes of gene regulators [17][18][19]. miRNA molecules can regulate genes at the post-transcriptional level by specifically recognising and affecting messenger RNA (mRNA), depending on the degree of homology with the targeted sequence [20].…”

Generation and modulation of chemosensory behaviors in C. elegans

“…On the other hand, while both the left and right AWC neurons sense benzaldehyde, either the left or the right AWC neuron responds to the volatile odorant butanone, and the other neuron responds to 2,3-pentanedione [71,99] (Table 1). The advantages of assigning the sensory functions stochastically as in the AWC neurons [100], or via a developmentally hardwired mechanism as for the ASE neurons [101][102][103] is not immediately obvious. A suggestion from these findings is that other chemosensory neuron types are likely to also exhibit left/right functional diversification, essentially doubling the sensory neuron repertoire.…”

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

“…Recent studies have revealed that miRNAs are involved in multiple biological pathways in a variety of animals. In C. elegans and Drosophila, miRNAs have been shown to affect a number of biological processes including developmental timing [5], left/right asymmetric neuronal cell fate [6,7], programmed cell death [8], muscle development [9], and fat metabolism [10]. In mammals, miRNAs have been implicated in a broad range of processes including hematopoietic lineage differentiation, developmental patterning, heart and skeletal muscle differentiation and function, insulin secretion, and immune function [11][12][13][14][15][16][17][18][19][20][21].…”