title: Lysophosphatidic acid differentially regulates axonal mRNA translation through 5'UTR elements.
abstract: Sensory neurons transport a complex population of mRNAs into their axons, including many encoding ER chaperone proteins. Transport of the mRNA encoding the ER chaperone protein calreticulin is regulated through 3'UTR elements. In other cellular systems, translation of chaperone protein mRNAs can be regulated by ER stress. Here, we have asked if the translation of axonal calreticulin mRNA is regulated in a different manner than its transport into axons. Treatment with lysophosphatidic acid, which is known to trigger axon retraction and stimulate ER Ca(2+) release, caused a translation-dependent increase in axonal calreticulin protein levels. RNA sequences in the 5'UTR of calreticulin confer this translational control through a mechanism that requires an inactivating phosphorylation of eIF2α. In contrast to calreticulin, these signaling events do not activate axonal translation through β-actin's 5'UTR. Together, these data indicate that stimulation of ER stress can regulate specificity of localized mRNA translation through 5'UTR elements.
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE USA.
authors.forename: Deepika
authors.initials: D
authors.lastname: Vuppalanchi
authors.forename: Tanuja T
authors.initials: TT
authors.lastname: Merianda
authors.forename: Christopher
authors.initials: C
authors.lastname: Donnelly
authors.forename: Almudena
authors.initials: A
authors.lastname: Pacheco
authors.forename: Gervan
authors.initials: G
authors.lastname: Williams
authors.forename: Soonmoon
authors.initials: S
authors.lastname: Yoo
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Ratan
authors.forename: Dianna E
authors.initials: DE
authors.lastname: Willis
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
mesh_terms: D020121:5' Untranslated Regions / Q000187:drug effects*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D037282:Calreticulin / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D008246:Lysophospholipids / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020121:5' Untranslated Regions; D037282:Calreticulin; D008246:Lysophospholipids; D012333:RNA, Messenger; C032881:lysophosphatidic acid