Micrornas 9a, 9b, 9c And 315 Regulate Expression Of A Reporter For The Neuronal Microtubule-Associated Protein Futsch/map1b

Fragile X syndrome (FXS) is the most common form of inherited mental retardation in humans. FXS is caused by loss of the Fragile X Mental Retardation Protein (FMRP), an important regulator of neuronal mRNA translation. Patients with FXS display cognitive deficits including memory problems. Protein synthesis-dependent long-term changes in synaptic plasticity are involved in the establishment and maintenance of long-term memory. One prevalent theory of FXS pathology predicts that FMRP is required to negatively regulate the translation of important mRNAs at the synapse. We are investigating microRNAs (miRNAs) as a potential regulator of synaptic FMRP-regulated mRNAs that have previously been described as being crucial to the process of synaptic plasticity. The general hypothesis underlying this thesis is that FMRP may negatively regulate the expression of futsch (the Drosophila homologue of the microtubule-associated protein gene MAP1B) via the miRNA pathway. The first step we took in testing this hypothesis was to confirm that futsch is subject to miRNA-mediated translational control. Using in silico target analysis, we predicted that several neuronally expressed miRNAs target the futsch mRNA 3'UTR and repress expression of Futsch protein. Then, using an in vitro luciferase reporter system, we showed that miR-315 and members of the miR-9 family selectively down-regulated futsch reporter translation. We have confirmed by site- directed mutagenesis that the miRNA interaction with the futsch 3'UTR is specific to the miRNA seed region binding site. Interestingly, reduction of FMRP levels by RNAi had no effect on futsch 3'UTR reporter expression. Together, these data suggest regulation of futsch expression by the miRNA pathway might be independent of FMRP activity. However, additional experiments need to be completed to confirm these preliminary results.

The southern reporter.

Vols. 6-142: Permanent ed.

Crop reporter.

Crop reporter.

Hearing; in the matter of the minimum wage recommendations of Special Industry Committee no. 17-D for the tobacco industry in Puerto Rico. September 6-8, 1955. Reporter: James A. Brownlee.

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The Western law reporter (Canada) and index-digest

Editors: 1905-Sept. 14, 1914, E.B. Brown; Sept. 21, 1914-May 1915, L.S. Le Vernois; June 1915-1916, E.K. Williams

The Ontario weekly reporter and index-digest

Publisher and sub-title vary: The Ontario weekly reporter and digest-index ... Toronto, Law books limited, 1916-17

The Code reporter.

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Transcript : Regional Public Meetings on the Resource conservation and recovery act of 1976, February 28 and March 1, 1977, Pittsburgh, Pa., [proceedings] ... transcribed by the official reporter, with handwritten corrections by the Office of Solid Waste.

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Transcript : Regional Public Meetings on the Resource conservation and recovery act of 1976, February 15 and 16, 1977, Kansas City, Mo., [proceedings] ... transcribed by the official reporter, with handwritten corrections by the Office of Solid Waste.

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