Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: FMRP activates the translation of large autism/intellectual disability proteins and stimulates N-end rule E3 ligase Poe/UBR4 production within puromycin-sensitive RNP particles Mutations in Fmr1, encoding the RNA binding protein FMRP, are leading causes of intellectual disability, autism, and female infertility, but FMRPs mechanism of action is controversial. In contrast to its previously postulated function as a translation repressor acting by stalling elongation, we recently found that FMRP activates translation initiation of large proteins in Drosophila oocytes up to [~]2-fold. We report here that FMRPs function as a translational activator is conserved in the mammalian brain. Reanalysis of mouse cortex ribosome profiling data shows that translation of large proteins in Fmr1 mutants is down-regulated 2.0-1.2-fold; ribosome stalling appears not to influence FMRP target protein translation in either cortex or oocyte tissue. Consistent with an activator function, most FMRP targets are associated with clinical syndromes when reduced, but not when over-expressed. Fmr1-dependent translation of one target, the N-end rule E3 ligase Poe/UBR4, occurs in microscopically visible ribonucleoprotein particles. These "Poe particles" require FMRP for their formation, are distinct from P bodies, and depend on actively elongating ribosomes, as indicated by their dissolution following a brief puromycin treatment. N-end rule-mediated proteolysis via Poe/UBR4 restrains cell growth and limits MAPK signaling in nervous tissue. Thus, loss of FMRP reduces production of an important growth repressor.
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The categories of this paper are: systems
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The categories of this paper are: neuroscience
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The categories of this paper are: physiology
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The categories of this paper are: synthetic
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The categories of this paper are: behavior
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The categories of this paper are: evolutionary
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The categories of this paper are: pathology
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The categories of this paper are: bioengineering
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The categories of this paper are: developmental
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The categories of this paper are: pharmacology
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The categories of this paper are: and
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The categories of this paper are: education
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The categories of this paper are: biophysics
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The categories of this paper are: genomics
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The categories of this paper are: toxicology
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The categories of this paper are: biology