Turner MJ et al. (2014) Cell Cycle "Autoregulation of lin-4 microRNA transcription by RNA activation (RNAa) in C. elegans."

Turner MJ, Jiao AL, Slack FJ

[Cell Cycle, 2014]

The conserved lin-4 microRNA (miRNA) regulates the proper timing of stem cell fate decisions in C. elegans by regulating stemness genes such as lin-14 and lin-28. (1)(-) (3) While lin-4 is upregulated toward the end of the first larval stage and functions as an essential developmental timing "switch", little is known about how lin-4 expression is regulated. (4) Here we show that in C. elegans hypodermal seam cells, transcription of lin-4 is positively regulated by lin-4 itself. In these cells, lin-4 activates its own transcription through a conserved lin-4-complementary element (LCE) in its promoter. We further show that lin-4 is required to recruit RNA polymerase II to its own promoter, and that lin-4 overexpression is sufficient for autoactivation. Finally, we show that a protein complex specifically binds the LCE in vitro, and that mutations that abolish this binding also reduce the in vivo expression of a plin-4:GFP reporter. Thus, we describe the first in vivo evidence of RNA activation (RNAa) by an endogenous miRNA, and provide new insights into an elegant autoregulatory mechanism that ensures the proper timing of stem cell fate decisions in development.

Turner MJ et al. (2019) Dev Comp Immunol "Avoidance behavior independent of innate-immune signaling seen in Caenorhabditis elegans challenged with Bacillus anthracis."

Bavari S, Stahl C, Turner MJ, Spellman AC, Cox JK

[Dev Comp Immunol, 2019]

Small organisms, like the nematode C. elegans, are emerging as insightful models in which to study host/pathogen interactions and the evolving interplay between host defenses and microbial offenses. In C. elegans the innate immune response has been shown to be connected to the DAF-2 insulin/insulin-like growth factor 1 (IGF-1) signal pathway, a critical transduction pathway that mediates stress response in the worms via the DAF-16 FOXO/forkhead transcription factor. Our studies of the C. elegans' phenotypes that are associated with behavioral innate immune response (avoidance behavior) and IGF-1 signaling perturbations (lifespan effects) led us to question the cause of the avoidance behavior observed when C. elegans are challenged with B. anthracis. While worms indeed avoid B. anthracis, and this behavior seems to be partly tied to IGF-1 signaling, the bacteria have neither nematocidal nor visible pathogenic effects on the worms. In fact, worms fed B. anthracis alone exhibit extended lifespans. We demonstrate that the extended lifespan phenotype seen in worms fed B. anthracis is likely the result of calorie restriction, and that worms do not eat B. anthracis even when avoidance behaviors have been suppressed. We further demonstrate a large time lag between the onset of avoidance behavior (which occurs upon contact with B. anthracis), and the induction of IGF-1 signaling (which occurs much later) in worms fed B. anthracis. Taken together, our data demonstrate behavioral avoidance that does not appear to be linked to a measurable immune response. We propose that, in some situations, avoidance behaviors categorized as immunological might be more accurately described as broad foraging behaviors induced in worms presented with a non-preferred food choice, or with a food choice that is either difficult or impossible for the worms to ingest.

Schaeffer JM et al. (1989) Biochem J "MK-801 is a potent nematocidal agent. Characterization of MK-801 binding sites in Caenorhabditis elegans."

Turner MJ, Bergstrom AR, Schaeffer JM

[Biochem J, 1989]

MK-801, an N-methyl-D-aspartate antagonist in mammalian brain tissue, is a potent nematocidal agent. Specific MK-801 binding sites have been identified and characterized in a membrane fraction prepared from the free-living nematode Caenorhabditis elegans. The high-affinity MK-801 binding site has an apparent dissociation constant, Kd, of 225 nM. Unlike the MK-801 binding site in mammalian tissues, the C. elegans binding site is not effected by glutamate or glycine, and polyamines are potent inhibitors of specific MK-801 binding.

Bichai F et al. (2009) Water Res "Protection against UV disinfection of E. coli bacteria and B. subtilis spores ingested by C. elegans nematodes."

Barbeau B, Bichai F, Payment P

[Water Res, 2009]

Nematodes, which occur abundantly in granular media filters of drinking water treatment plants and in distribution systems, can ingest and transport pathogenic bacteria and provide them protection against chemical disinfectants. However, protection against UV disinfection had not been investigated to date. In this study, Caenorhabditis elegans nematodes (wild-type strain N2) were allowed to feed on Escherichia coli OP50 and Bacillus subtilis spores before being exposed to 5 and 40 mJ/cm(2) UV fluences, using a collimated beam apparatus (LP, 254 nm). Sonication (15 W, 60s) was used to extract bacteria from nematode guts following UV exposure in order to assess the amount of ingested bacteria that resisted the UV treatment using a standard culture method. Bacteria located inside the gut of C. elegans were shown to benefit from a significant protection against UV. Approximately 15% of the applied UV fluence of 40 mJ/cm(2) (as typically used in WTP) was found to reach the bacteria located inside nematode guts based on the inactivation of recovered bacteria (2.7 log reduction of E. coli bacteria and 0.7 log reduction of B. subtilis spores at 40 mJ/cm(2)). To our knowledge, this study is the first demonstration of the protection effect of bacterial internalization by higher organisms against UV treatment, using the specific case of E. coli and B. subtilis spores ingested by C. elegans.

Schaeffer JM et al. (1990) Pesticide Biochemistry & Physiology "Identification of glutamate-binding sites in Caenorhabditis elegans."

Wilson KE, Turner MJ, White TM, Schaeffer JM, Bergstrom AR

[Pesticide Biochemistry & Physiology, 1990]

Waldispuhl J et al. (2007) J Comput Biol "Computing the partition function and sampling for saturated secondary structures of RNA, with respect to the Turner energy model."

Waldispuhl J, Clote P

[J Comput Biol, 2007]

An RNA secondary structure is saturated if no base pairs can be added without violating the definition of secondary structure. Herewe describe a new algorithm, RNAsat, which for a given RNA sequence a, an integral temperature 0 </= T </= 100 in degrees Celsius, and for all integers k, computes the Boltzmann partition function , where the sum is over all saturated secondary structures of a which have exactly k base pairs, R is the universal gas constant and E(S) denotes the free energy with respect to the Turner nearest neighbor energy model. By dynamic programming, we compute simultaneously for all values of k in time O(n (5)) and space O(n (3)).Additionally, RNAsat computes the partition function , where the sum is over all secondary structures of a which have k base pairs; the latter computation is performed simultaneously for all values of k in O(n (4)) time and O(n (3)) space. Lastly, using the partition function [resp. ] with stochastic backtracking, RNAsat rigorously samples the collection of saturated secondary structures [resp. secondary structures] having k base pairs; for this provides a parametrized form of Sfold sampling (Ding and Lawrence, 2003). Using RNAsat, (i) we compute the ensemble free energy for saturated secondary structures having k base pairs, (ii) show cooperativity of the Turner model, (iii) demonstrate a temperature-dependent phase transition, (iv) illustrate the predictive advantage of RNAsat for precursor microRNA cel-mir-72 of C. elegans and for the pseudoknot PKB 00152 of Pseudobase (van Batenburg et al., 2001), (v) illustrate the RNA shapes (Giegerich et al., 2004) of sampled secondary structures [resp. saturated structures] having exactly k base pairs. A web server for RNAsat is under construction at bioinformatics.bc.edu/clotelab/RNAsat/.

Farooqui A et al. (2018) Sci Rep "Assessment of the key regulatory genes and their Interologs for Turner Syndrome employing network approach."

Ahmed MM, Malik MZ, Farooqui A, Tazyeen S, Ali S, Ishrat R, Alam A

[Sci Rep, 2018]

Turner Syndrome (TS) is a condition where several genes are affected but the molecular mechanism remains unknown. Identifying the genes that regulate the TS network is one of the main challenges in understanding its aetiology. Here, we studied the regulatory network from manually curated genes reported in the literature and identified essential proteins involved in TS. The power-law distribution analysis showed that TS network carries scale-free hierarchical fractal attributes. This organization of the network maintained the self-ruled constitution of nodes at various levels without having centrality-lethality control systems. Out of twenty-seven genes culminating into leading hubs in the network, we identified two key regulators (KRs) i.e. KDM6A and BDNF. These KRs serve as the backbone for all the network activities. Removal of KRs does not cause its breakdown, rather a change in the topological properties was observed. Since essential proteins are evolutionarily conserved, the orthologs of selected interacting proteins in C. elegans, cat and macaque monkey (lower to higher level organisms) were identified. We deciphered three important interologs i.e. KDM6A-WDR5, KDM6A-ASH2L and WDR5-ASH2L that form a triangular motif. In conclusion, these KRs and identified interologs are expected to regulate the TS network signifying their biological importance.