iPS cell-derived NeuronsGreen: MAP2 – neuronal markerRed: DCP1A – P-body marker
iPS cell-derived neurons
Green: MAP2 – neuronal marker
Red: DCP1A – P-body marker
Courtesy: Dr. Deivid Rodrigues

Post-transcriptional gene regulation

 

Post-transcriptional gene regulation

A new direction for our research concerns post-transcriptional regulation in stem cell and neurons.  We contributed to Ben Blencowe’s lab discovery that knockdown of the MBNL splicing family promotes reprogramming.  In addition, many genes important for neuron function are highly transcribed in ES and iPS cells, but the mRNA is not efficiently translated into protein until neurons are made.  We first investigated post-transcriptional pathways that regulate the MECP2 transcript and protein accumulation with an emphasis on RNA binding proteins that recognize elements in the 3’UTR. Together with the Blencowe lab, we are examining genome-wide regulation of transcript stability and ribosome engagement. We are also initiating studies of activity-dependent translation in control and ASD neurons.  These RNA biology projects are funded by CIHR, MbD, SFARI and the POND network, and were initiated with funds from OIRM and IRSF.

Selected Publications

  1. Rodrigues D.C+, Mufteev M+, Yuki KE, Narula A, Wei W, Piekna A, Liu J, Pasceri P, Rissland OS, Wilson MD, Ellis J. 2023. Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models. +Co-first authors. Nature Communications,14:1896.
  2. Murtaza N, Cheng AA, Brown CO, Meka DP, Hong S, Uy JA, El-Hajjar J, Pipko N, Unda BK, Schwanke B, Xing S, Thiruvahindrapuram B, Engchuan W, Trost B, Deneault E, Calderon de Anda F, Doble BW, Ellis J, Anagnostou E, Bader GD, Scherer SW, Lu Y, Singh KK. 2022. Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. Cell Reports, 41:111678
  3. Subramanian A, Hall M, Hou H, Mufteev M, Yu B, Yuki KE, Nishimura H, Sathaseevan A, Lant B, Zhai B, Ellis J, Wilson MD, Daugaard M, Derry WB. 2021. Alternative polyadenylation is a determinant of oncogenic Ras function. Science Advances 7: eabh0562.
  4. Byres LP, Mufteev M, Yuki KE, Wei W, Piekna A, Wilson MD, Rodrigues DC* and Ellis J*. 2021. Identification of TIA-1 mRNA targets during human neuronal development. *Co-corresponding authors. Molecular Biology Reports, 48:6349-6361
  5. Rodrigues D.C.*, Mufteev M, Ellis J. 2020. Quantification of mRNA ribosomal engagement in human neurons using parallel translating ribosome affinity purification (TRAP) and RNA sequencing. *Corresponding author. STAR Protocols, 2:100229.
  6. Rodrigues DC, Mufteev M, Ellis J. 2020. Regulation, diversity and function of MECP2 exon and 3’UTR isoforms. Human Molecular Genetics, ddaa154.
  7. Rodrigues DC, Harvey EM, Suraj R, Erickson SL, Mohammad L, Ren M, Liu H, He G, Kaplan DR, Ellis J, Yang G. 2020. Methylglyoxal couples metabolic and translational control of Notch signalling in mammalian neural stem cells. Nat Commun. 24;11(1):2018
  8. Rodrigues DC, Mufteev M, Weatheritt RJ, Djuric U, Ha KCH, Ross PJ, Wei W, Piekna A, Sartori MA, Byres L, Mok RSF, Zaslavsky K, Pasceri P, Diamandis P, Morris Q, Blencowe BJ, Ellis J. 2020. Shifts in Ribosome Engagement Impact Key Gene Sets in Neurodevelopment and Ubiquitination in Rett Syndrome Neurons. Cell Reports 30:4179-96.
  9. A. Narula, J. Ellis, J.M. Taliaferro and O.S. Rissland. 2019. Coding regions affect mRNA Stability in Human Cells. RNA 25:1751-64.
  10. Djuric U, Rodrigues DC, Batruch I, Ellis J, Shannon P, Diamandis P. 2017. Spatiotemporal proteomic profiling of human cerebral development. Djuric U, et al. Molecular and cellular proteomics. 16(9):1548-1562.
  11. Rodrigues DC, Kim DS, Yang G, Zaslavsky K, Ha KC, Mok RS, Ross PJ, Zhao M, Piekna A, Wei W, Blencowe BJ, Morris Q, Ellis J. 2016. MECP2 is post-transcriptionally regulated during human neurodevelopment by combinatorial action of RNA-binding proteins and miRNAs. Cell Reports. 17(3); 720-734.
  12. Han H, Irimia M, Ross PJ, Sung HK, Alipanahi B, David L, Golipour A, Gabut M, Michael IP, Nachman EN, Wang E, Trcka D, Thompson T, O’Hanlon D, Slobodeniuc V, Barbosa-Morais NL, Burge CB, Moffat J, Frey BJ, Nagy A, Ellis J, Wrana JL, and Blencowe BJ. 2013. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature. 498(7453):241-5.