%0 Journal Article %J Dev Biol %D 2022 %T DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration. %A Sarkar, Souradeep R %A Dubey, Vinay Kumar %A Jahagirdar, Anusha %A Lakshmanan, Vairavan %A Haroon, Mohamed Mohamed %A Sowndarya, Sai %A Sowdhamini, Ramanathan %A Palakodeti, Dasaradhi %X

Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputation-induced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.

%B Dev Biol %V 488 %P 11-29 %8 2022 May 04 %G eng %R 10.1016/j.ydbio.2022.04.011 %0 Journal Article %J Proc Natl Acad Sci U S A %D 2021 %T Discovery of a body-wide photosensory array that matures in an adult-like animal and mediates eye-brain-independent movement and arousal. %A Shettigar, Nishan %A Chakravarthy, Anirudh %A Umashankar, Suchitta %A Lakshmanan, Vairavan %A Palakodeti, Dasaradhi %A Gulyani, Akash %X

The ability to respond to light has profoundly shaped life. Animals with eyes overwhelmingly rely on their visual circuits for mediating light-induced coordinated movements. Building on previously reported behaviors, we report the discovery of an organized, eye-independent (extraocular), body-wide photosensory framework that allows even a head-removed animal to move like an intact animal. Despite possessing sensitive cerebral eyes and a centralized brain that controls most behaviors, head-removed planarians show acute, coordinated ultraviolet-A (UV-A) aversive phototaxis. We find this eye-brain-independent phototaxis is mediated by two noncanonical rhabdomeric opsins, the first known function for this newly classified opsin-clade. We uncover a unique array of dual-opsin-expressing photoreceptor cells that line the periphery of animal body, are proximal to a body-wide nerve net, and mediate UV-A phototaxis by engaging multiple modes of locomotion. Unlike embryonically developing cerebral eyes that are functional when animals hatch, the body-wide photosensory array matures postembryonically in "adult-like animals." Notably, apart from head-removed phototaxis, the body-wide, extraocular sensory organization also impacts physiology of intact animals. Low-dose UV-A, but not visible light (ocular-stimulus), is able to arouse intact worms that have naturally cycled to an inactive/rest-like state. This wavelength selective, low-light arousal of resting animals is noncanonical-opsin dependent but eye independent. Our discovery of an autonomous, multifunctional, late-maturing, organized body-wide photosensory system establishes a paradigm in sensory biology and evolution of light sensing.

%B Proc Natl Acad Sci U S A %V 118 %8 2021 May 18 %G eng %N 20 %R 10.1073/pnas.2021426118 %0 Journal Article %J EMBO Rep %D 2019 %T Dynamic expression of tRNA-derived small RNAs define cellular states. %A Krishna, Srikar %A Yim, Daniel Gr %A Lakshmanan, Vairavan %A Tirumalai, Varsha %A Koh, Judice Ly %A Park, Jung Eun %A Cheong, Jit Kong %A Low, Joo Leng %A Lim, Michelle Js %A Sze, Siu Kwan %A Shivaprasad, Padubidri %A Gulyani, Akash %A Raghavan, Srikala %A Palakodeti, Dasaradhi %A DasGupta, Ramanuj %X

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell-state transitions remain unclear. Expression analysis of tsRNAs in distinct heterologous cell and tissue models of stem vs. differentiated states revealed a differentiation-dependent enrichment of 5'-tsRNAs. We report the identification of a set of 5'-tsRNAs that is upregulated in differentiating mouse embryonic stem cells (mESCs). Notably, interactome studies with differentially enriched 5'-tsRNAs revealed a switch in their association with "effector" RNPs and "target" mRNAs in different cell states. We demonstrate that specific 5'-tsRNAs can preferentially interact with the RNA-binding protein, Igf2bp1, in the RA-induced differentiated state. This association influences the transcript stability and thereby translation of the pluripotency-promoting factor, c-Myc, thus providing a mechanistic basis for how 5'-tsRNAs can modulate stem cell states in mESCs. Together our study highlights the role of 5'-tsRNAs in defining distinct cell states.

%B EMBO Rep %V 20 %P e47789 %8 2019 Jul %G eng %N 7 %R 10.15252/embr.201947789