@article{4473a74fc3be48c8b8c54a082538babb,
title = "Loss of tsc1 in cerebellar purkinje cells induces transcriptional and translation changes in fmrp target transcripts",
abstract = "Tuberous sclerosis complex (TSC) is a genetic disorder that is associated with multiple neurological manifestations. Previously, we demonstrated that Tsc1 loss in cerebellar Purkinje cells (PCs) can cause altered social behavior in mice. Here, we performed detailed transcriptional and translational analyses of Tsc1-deficient PCs to understand the molecular alterations in these cells. We found that target transcripts of the Fragile X Mental Retardation Protein (FMRP) are reduced in mutant PCs with evidence of increased degradation. Surprisingly, we observed unchanged ribosomal binding for many of these genes using translating ribosome affinity purification. Finally, we found that multiple FMRP targets, including SHANK2, were reduced, suggesting that compensatory increases in ribosomal binding efficiency may be unable to overcome reduced transcript levels. These data further implicate dysfunction of FMRP and its targets in TSC and suggest that treatments aimed at restoring the function of these pathways may be beneficial.",
author = "Dalal, {Jasbir Singh} and Winden, {Kellen Diamond} and Salussolia, {Catherine Lourdes} and Maria Sundberg and Achint Singh and Pham, {Truc Thanh} and Pingzhu Zhou and Pu, {William T.} and Miller, {Meghan T.} and Mustafa Sahin",
note = "Funding Information: We would like to thank Elizabeth Bainbridge and Sarika Gurnani for help with mouse breeding. The Sahin lab has received grant funding from the U.S. Army Medical Research Tuberous Sclerosis Complex Research Program (W81XWH-15-1-0189). Boston Children?s Hospital Intellectual and Developmental Disabilities Research Center (BCH IDDRC, U54HD090255). JSD was supported by Roche Postdoctoral Fellowship (RPF) Program. KDW is funded by the Neuroscience Research Training Scholarship from the American Academy of Neurology and NIH (5K08NS112598). CLS is funded by the CH/BIDMC/Harvard Medical School Neurology Resident Research Education Program NIH R25NS070682. Funding Information: We would like to thank Elizabeth Bainbridge and Sarika Gurnani for help with mouse breeding. The Sahin lab has received grant funding from the U.S. Army Medical Research Tuberous Sclerosis Complex Research Program (W81XWH-15-1-0189). Boston Children{\textquoteright}s Hospital Intellectual and Developmental Disabilities Research Center (BCH IDDRC, U54HD090255). JSD was supported by Roche Postdoctoral Fellowship (RPF) Program. KDW is funded by the Neuroscience Research Training Scholarship from the American Academy of Neurology and NIH (5K08NS112598). CLS is funded by the CH/BIDMC/Harvard Medical School Neurology Resident Research Education Program NIH R25NS070682. Publisher Copyright: {\textcopyright} Dalal et al.",
year = "2021",
month = jul,
doi = "10.7554/eLife.67399",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}