An environment to genome control loop using RNA interference processing of secreted Ala-tRNAs may regulate the C. elegans chemo-attractive behavior.

Alanine tRNAs (UGC) control the development of the innate and the environment-modulated acquired C. elegans chemo-attractive responses. Some Ala-tRNA isomers are required for the development of the chemo-attractive behavior (dev-tRNAs), while others (odor-tRNAs) are made as life-term olfactory imprints of early larval odor-exposures. dev-tRNAs and odor-tRNAs biosynthesis respectively require the tRNA modifying Elongator complex sub-units ELPC-3 and ELPC-1: while elpc-3 mutants are chemo-attraction deficients, elpc-1 mutants do not synthesize odor-tRNAs imprints. Feeding wild-type dev-tRNAs restore a wild-type behavior in elpc-3 mutants. Feeding purified odor-tRNAs enhances odor responses (positive imprinting) in adult wild-type worms, while it decreases odor responses (negative imprinting) in adult imprinting deficient elpc-1 mutants. Both positive and negative imprinting can be stably inherited in worm populations. Crossing experiments indicate that both behavioral phenotypes segregate as monogenic monoallelic alterations, following Mendelian inheritance rules. Co-culture and food conditioning suggest the developmental and the odor-specific regulatory Ala-tRNAs are released in worms environment. Commensal naive acquire odor-specific imprinting from odor-experienced, while co-culture together with wild-type animals fully rescues the chemo-attractive defects of the elpc-3 mutants. Worm to worm communication of imprinting require a number of RNA interference (RNAi) genes as the intestinal RNA transporter SID-2, the initial exogenous RNAi Dicer/RDE-1/DRH-1-2/RDE-4 complexe, and the RNA-dependent RNA polymerase RRF-3. Moreover, a male contribution of the 3-exonuclease ERI-1 activity determines whether olfactory imprints will be erased or stably fixed and inherited in worms progeny. The RNAi processing of externalized chemosensory regulatory Ala-tRNAs would generate small interfering tRNAs (si-tRNAs) able to target only tRNA complementary sequences present on worm genome, that is the tDNA genes and the transcription independent extra-TFIIIC sites. A model of control loop in which olfactory receptor expression levels in chemosensory neurons could be non-genetically but stably regulated via RNAi processing of secreted constitutive or environment-modified Ala-tRNAs is discussed.