The Kei-ichiro Maeda Memorial T&C Award Transcriptome-wide studies on mRNA tailing and investigation of stress responses in immune cells Jaechul Lim, D.V.M., Ph.D. College of Veterinary Medicine, Seoul National University, Rep. of Korea Sep 12, 2023
Postdoc College of Veterinary Medicine Ph.D.
Seoul National University
School of Biological Sciences Yale School of Medicine Department of Immunobiology 2005-2011
2017-2023 B.S./D.V.M.
Davalos et al., Cell, 2018
identifies the tag
AAAAAA
Read 2 determines the 3' end sequences •  Reanalysis of fluorescence signal to measure poly(A) length Chang*, Lim* et al., Mol Cell, 2014
1. TUT4 and TUT7 specifically uridylate deadenylated mRNAs and thereby facilitate global mRNA decay. 2.  mRNAs with short A tails (<~25 nt) lose PABP and instead gain a U-tail. 3. The oligo-U tail triggers mRNA decay by serving as a general mark that is recognized by downstream decay factors. Lim*, Ha*, Chang* et al., Cell, 2014
Poly(A)† mRNA 1. TENT4A/B add mixed tails (A >> G > C, U) to poly(A) mRNAs. 2. Non-adenosine residues slow down CNOT6L/7 deadenylases. 3. The mixed tail protects and stabilizes mRNAs from deadenylation. mRNA body decay Lim*, Kim*, Lee* et al., Science, 2018 Rapid deadenylation
TAIL-seq 3' adaptor mTAIL-seq 3' adaptor (hairpin) © Biotin $ Spacer ® Inverted dT (3'-3' linkage) ♈ 1′, 2′ -Dideoxyribose (abasic site) 😊 C3 spacer phosphoramidite Global poly(A) distribution → Fly oocytes and embryos → Dynamic poly(A) tail regulation in oocyte- to-embryo development Lim*, Lee* et al., Genes Dev, 2016
mRNA metabolism (Deadenylation, decay, and translation) Cell cycle regulation Lima et al., Nat Str Mol Biol, 2017 Yi*, Park* et al., Mol Cell, 2018 Eisen*, Eichhorn*, Subtelny* et al., Mol Cell, 2020 Xiang and Bartel, eLife, 2021 Park*, Yi*, Kim* et al., Mol Cell, 2016 Liu et al., iScience, 2020 Development (Oogenesis and embryogenesis) Lim*, Lee* et al., Genes Dev, 2016 Morgan*, Much* et al., Nature, 2017 Chang*, Yeo* et al., Mol Cell, 2018 Viral infection Batra*, Stark* et al., Nat Str Mol Biol, 2016 Kim*, Lee*, Jung*, Yeo* et al., Nat Str Mol Biol, 2020 T cell quiescence Hwang*, Lim* et al., Science, 2020
Modified from Sharma et al., Nat Rev Cancer, 2011
Btg1/2 double KO : Exit of quiescence 1. BTG1/2 promote global mRNA deadenylation and degradation in naive T cells. 2. Loss of Btg1/2 results in exit of T cell quiescence by increasing global mRNA levels. 3. Active mRNA turnover might be a crucial feature for maintaining quiescence.
Hwang*, Lim* et al., Science, 2020

Stress hormone (glucocorticoids)
1) Glucocorticoids induce natural IgE both in vivo and ex vivo without antigenic challenge. 2) Glucocorticoids reinforce CD40 signaling and are dependent on IL-4/STAT6. 3) Natural IgE-producing B cells are localized in mLNs in vivo. 4) Natural IgE induced by glucocorticoids may have a protective role in preventing allergic reactions. Lim*, Lin*, Hong* et al., J Exp Med, 2022
I will investigate how cells or animals adapt to stress conditions. 1. Animals have a variety of digestive systems. I aim to understand how immune cells maintain homeostasis, especially in the gut. I am interested in the role of immune cells when gut homeostasis is perturbed, such as dysbiosis or food poisoning. 2. In response to stress, some animals exhibit a highly stress-resistant state, like hibernation or dormancy. I am interested in the molecular mechanisms how cells or animals cope with extreme environmental conditions.
Collaborators RNomics Lab (SNU)   Flavell Lab (Yale)  Medzhitov Lab (Yale) V. Narry Kim
Minju Ha Mihye Lee Dongwan Kim Young-suk Lee
Yale School of Medicine Howard Hughes Medical Institute Human Frontier Science Program   Jane Coffin Childs Memorial Fund SNU/Institute for Basic Science Thank you!