EGGTART: A tool to visualize the dynamics of biophysical transport under the inhomogeneous l-TASEP

Erdmann-Pham, Dan D.; Son, Wonjun; Duc, Khanh Dao; Song, Yun S.

doi:10.1016/j.bpj.2021.02.004

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Elongation rates of control transcripts were greatly reduced at random to simulate a mutation inducing pauses in translation. These elongation rates were inputted into an implementation of the inhomogeneous ℓ-Totally Asymmetric Simple Exclusion Process (TASEP) ( Erdmann-Pham et al 2020 ; Erdmann-Pham et al 2021 ) model in Python. The inhomogeneous ℓ-TASEP model was used to determine if translation was initiation limited, elongation limited, or termination limited.…”

Section: Methodsmentioning

confidence: 99%

FMRP-dependent production of large dosage-sensitive proteins is highly conserved

et al. 2022

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Mutations in FMR1 are the most common heritable cause of autism spectrum disorder. FMR1 encodes an RNA-binding protein, FMRP, which binds to long, autism-relevant transcripts and is essential for normal neuronal and ovarian development. In contrast to the prevailing model that FMRP acts to block translation elongation, we previously found that FMRP activates the translation initiation of large proteins in Drosophila oocytes. We now provide evidence that FMRP-dependent translation is conserved and occurs in the mammalian brain. Our comparisons of the mammalian cortex and Drosophila oocyte ribosome profiling data show that translation of FMRP-bound mRNAs decreases to a similar magnitude in FMRP-deficient tissues from both species. The steady-state levels of several FMRP targets were reduced in the Fmr1 KO mouse cortex, including a ∼50% reduction of Auts2, a gene implicated in an autosomal dominant autism spectrum disorder. To distinguish between effects on elongation and initiation, we used a novel metric to detect the rate-limiting ribosome stalling. We found no evidence that FMRP target protein production is governed by translation elongation rates. FMRP translational activation of large proteins may be critical for normal human development, as more than 20 FMRP targets including Auts2 are dosage sensitive and are associated with neurodevelopmental disorders caused by haploinsufficiency.

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Section: Methodsmentioning

confidence: 99%

FMRP-dependent production of large dosage-sensitive proteins is highly conserved

et al. 2022

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show abstract

“…This behavior has been thoroughly characterized using stochastic models of translation, such as the inhomogeneous l-TASEP model ( Erdmann-Pham et al. 2020 , 2021 ), and has been observed in ribosome profiling experiments done on cells that have undergone elongation limitation inducing treatments ( Woolstenhulme et al., 2015 ; Fradejas-Villar et al., 2017 ). Our metric is determined using the K-S statistic, which is traditionally calculated as part of the K-S test, a well-documented test for determining if two distributions are statistically equivalent.…”

Section: Before You Beginmentioning

confidence: 99%

“…As such, the K-S statistic will be relatively high when comparing distributions of transcripts which are initiation limited under one condition and elongation limited in the other. Read density data were created using simulations based on the inhomogeneous l-TASEP model ( Erdmann-Pham et al., 2021 ). …”

Section: Before You Beginmentioning

confidence: 99%