Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells

Abstract

Highlights d NAT1 is required for the self-renewal and neural differentiation of primed PSCs d Loss of NAT1 induced aberrant HERV-H expression in human PSCs d TUT7 contributes to regulate precise expression of HERV-Hs in human PSCs d NAT1 promotes the translation of TUT7

DAP5 enables translation re-initiation on structured messenger RNAs

“…We find that DAP5-dependent re-initiation is required for translation of the (Nousch et al, 2007;Sugiyama et al, 2017;Takahashi et al, 2020;Yamanaka et al, 2000;Yoffe et al, 2016;Yoshikane et al, 2007). As several DAP5 targets are known oncogenes and disease-associated genes, future investigations are required to unveil the biological and functional implications of re-initiation in pathological settings.…”

“…It is made The copyright holder for this preprint this version posted January 21, 2021. ; https://doi.org/10.1101/2021.01.21.427569 doi: bioRxiv preprint dependent translational control of specific signalling components and enzymes that usually have dose-dependent functions efficiently regulates the overall strength of particular signalling pathways in response to stimuli, enabling cells to adapt or adopt different states according to the surrounding environment. Underscoring the physiological importance of DAP5 and re-initiation are the observations that DAP5 deletion in animals results in early embryonic lethality by blocking stem-cell differentiation (Nousch et al, 2007;Sugiyama et al, 2017;Takahashi et al, 2020;Yamanaka et al, 2000;Yoffe et al, 2016;Yoshikane et al, 2007). As several DAP5 targets are known oncogenes and disease-associated genes, future investigations are required to unveil the biological and functional implications of re-initiation in pathological settings.…”

“…Alternatively, DAP5 was proposed to initiate non-canonical translation via the assembly of cap-bound complexes with proteins other than eIF4E (Bukhari et al, 2016;de la Parra et al, 2018). As DAP5 is an ubiquitously expressed and abundant protein known to control the expression of genes required for stem cell differentiation and embryonic development (Nousch et al, 2007;Sugiyama et al, 2017;Takahashi et al, 2020;Yamanaka et al, 2000;Yoffe et al, 2016;Yoshikane et al, 2007), understanding its mode of action is important for elucidating the mechanisms that drive non-canonical translation.…”

The pluripotent stem cell-specific transcript ESRG is dispensable for human pluripotency

“…Previous studies showed that HERV-H expression regulates the neural differentiation potential of human PSCs [10, 15, 26]. Thus, in addition to the random differentiation by EB formation, we tested whether ESRG contributes to the directed differentiation of PSCs into NPCs by the dual SMAD inhibition method [27, 28].…”

“…Primed PSCs were differentiated into expandable NPCs by using the STEMdiff SMADi Neural Induction Kit (Stem Cell Technologies) as previously described [26–28]. In brief, primed PSCs were maintained on a Matrigel (Corning)-coated plate in mTeSR1 media (Stem Cell Technologies) prior to the NPC induction.…”