RiboCop
Differences between dorsal root and trigeminal ganglion nociceptors in mice revealed by translational profiling
Salim Megat, Pradipta R. Ray, Diana Tavares-Ferreira, Jamie K. Moy, Ishwarya Sankaranarayanan, Andi Wanghzou, Tzu Fang Lou, Paulino Barragan-Iglesias, Zachary T. Campbell, Gregory Dussor, Theodore J. Price
The Journal of Neuroscience, doi:10.1523/JNEUROSCI.2663-18.2019
Nociceptors located in the TG and DRG are the primary sensors of damaging or potentially damaging stimuli for the head and body, respectively, and are key drivers of chronic pain states. While nociceptors in these two tissues show a high degree of functional similarity, there are important differences in their development lineages, their functional connections to the central nervous system, and recent genome-wide analyses of gene expression suggest that they possess some unique genomic signatures. Here, we used translating ribosome affinity purification (TRAP) to comprehensively characterize and compare mRNA translation in Scn10a-positive nociceptors in the TG and DRG of male and female mice. This unbiased method independently confirms several findings of differences between TG and DRG nociceptors described in the literature but also suggests preferential utilization of key signaling pathways. Most prominently, we provide evidence that translational efficiency in mechanistic target of rapamycin (mTOR)-related genes is higher in the TG compared to DRG while several genes associated with the negative regulator of mTOR, AMPK activated protein kinase (AMPK), have higher translational efficiency in DRG nociceptors. Using capsaicin as a sensitizing stimulus we show that behavioral responses are greater in the TG region and this effect is completely reversible with mTOR inhibition. These findings have implications for the relative capacity of these nociceptors to be sensitized upon injury. Altogether, our data provide a comprehensive, comparative view of transcriptome and translatome activity in TG and DRG nociceptors that enhances our understanding of nociceptor biology.
SIGNIFICANCE STATEMENT
The DRG and TG provide sensory information from the body and head, respectively. Nociceptors in these tissues are critical first neurons in the pain pathway. Injury to peripheral neurons in these tissues can cause chronic pain. Interestingly, clinical and preclinical findings support the conclusion that injury to TG neurons is more likely to cause chronic pain and chronic pain in the TG area is more intense and more difficult to treat. We used TRAP technology to gain new insight into potential differences in the translatomes of DRG and TG neurons. Our findings demonstrate previously unrecognized differences between TG and DRG nociceptors that provide new insight into how injury may differentially drive plasticity states in nociceptors in these two tissues.
Features RiboCop rRNA Depletion Kit V1.2 (Human/Mouse/Rat) and QuantSeq 3’ mRNA-Seq Library Prep Kit FWD for Illumina
OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development
Joel Hrit, Leeanne Goodrich, Cheng Li, Bang-An Wang, Ji Nie, Xiaolong Cui, Elizabeth Allene Martin, Eric Simental, Jenna Fernandez, Monica Yun Liu, Joseph R Nery, Rosa Castanon, Rahul M Kohli, Natalia Tretyakova, Chuan He, Joseph R Ecker, Mary Goll, Barbara Panning
TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.
Features RiboCop rRNA Depletion Kit V1.2 (Human/Mouse/Rat) and SENSE Total RNA-Seq Library Prep Kit
IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner
Simon Müller, Markus Glaß, Anurag K Singh, Jacob Haase, Nadine Bley, Tommy Fuchs, Marcell Lederer, Andreas Dahl, Huilin Huang, Jianjun Chen, Guido Posern, Stefan Hüttelmaier
Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation* REVIEW
Ethan Edward Ford,Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alex de Mendoza, Peggy J. Farnham, Pilar Blancafort, Ryan Lister