Interactions of noncanonical motifs with hnRNP A2 promote activity-dependent RNA transport in neurons.
A key determinant of neuronal functionality and plasticity is the targeted delivery of select ribonucleic acids (RNAs) to synaptodendritic sites of protein synthesis. In this paper, we ask how dendritic RNA transport can be regulated in a manner that is informed by the cell's activity status. We describe a molecular mechanism in which inducible interactions of noncanonical RNA motif structures with targeting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 form the basis for activity-dependent dendritic RNA targeting. High-affinity interactions between hnRNP A2 and conditional GA-type RNA targeting motifs are critically dependent on elevated Ca(2+) levels in a narrow concentration range. Dendritic transport of messenger RNAs that carry such GA motifs is inducible by influx of Ca(2+) through voltage-dependent calcium channels upon β-adrenergic receptor activation. The combined data establish a functional correspondence between Ca(2+)-dependent RNA-protein interactions and activity-inducible RNA transport in dendrites. They also indicate a role of genomic retroposition in the phylogenetic development of RNA targeting competence.
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203.
Ilham A
IA
Muslimov
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203.
Aliya
A
Tuzhilin
Advanced Medical and Dental Institute, Universiti Sains Malaysi, 13200 Kepala Batas, Penang, Malaysia.
Thean Hock
TH
Tang
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203.
Robert K S
RK
Wong
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203.
Riccardo
R
Bianchi
The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, and Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203 henri.tiedge@downstate.edu.
Henri
H
Tiedge
D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D015220:Calcium Channels / Q000235:genetics; D020013:Calcium Signaling / Q000235:genetics; D003712:Dendrites / Q000502:physiology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology; D023281:Genomics; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D061251:Primary Cell Culture; D034443:RNA Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018626:Retroelements / Q000235:genetics; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism; D000091346:Tripeptidyl-Peptidase 1; D014404:Tubulin / Q000235:genetics
D015220:Calcium Channels; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012333:RNA, Messenger; D018626:Retroelements; D000091346:Tripeptidyl-Peptidase 1; D014404:Tubulin; C439768:hnRNP A2; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases