Biomedical subjects

Tasneem Khanam

Publications and source records attributed to Tasneem Khanam.

3 recordsLinked to original sources

PubMed2006

Two primate-specific small non-protein-coding RNAs in transgenic mice: neuronal expression, subcellular localization and binding partners.

In a rare occasion a single chromosomal locus was targeted twice by independent Alu-related retroposon insertions, and in both cases supported neuronal expression of the respective inserted genes encoding small non-protein coding RNAs (npcRNAs): BC200 RNA in anthropoid primates and G22 RNA in the Lorisoidea branch of prosimians. To avoid primate experimentation, we generated transgenic mice to study neuronal expression and protein binding partners for BC200 and G22 npcRNAs. The BC200 gene, with sufficient upstream flanking sequences, is expressed in transgenic mouse brain areas comparable to those in human brain, and G22 gene, with upstream flanks, has a similar expression pattern. However, when all upstream regions of the G22 gene were removed, expression was completely abolished, despite the presence of intact internal RNA polymerase III promoter elements. Transgenic BC200 RNA is transported into neuronal dendrites as it is in human brain. G22 RNA, almost twice as large as BC200 RNA, has a similar subcellular localization. Both transgenically expressed npcRNAs formed RNP complexes with poly(A) binding protein and the heterodimer SRP9/14, as does BC200 RNA in human. These observations strongly support the possibility that the independently exapted npcRNAs have similar functions, perhaps in translational regulation of dendritic protein biosynthesis in neurons of the respective primates.

Animals↗

PubMed2005

Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP).

Regulated protein biosynthesis in dendrites of neurons might be a key mechanism underlying learning and memory. Neuronal dendritic BC1 RNA and BC200 RNA and similar small untranslated RNAs inhibit protein translation in vitro systems, such as rabbit reticulocyte lysate. Likewise, co-transfection of these RNAs with reporter mRNA suppressed translation levels in HeLa cells. The oligo(A)-rich region of all active small RNAs were identified as the RNA domains chiefly responsible for the inhibitory effects. Addition of recombinant human poly(A)-binding protein (PABP) significantly compensated the inhibitory effect of the small oligo(A)-rich RNA. In vivo, all BC1 RNA appears to be complexed with PABP. Nevertheless, in the micro-environment of dendritic spines of neuronal cells, BC1 RNPs or BC200 RNPs might mediate regulatory functions by differential interactions with locally limited PABP and/or directly or indirectly, with other translation initiation factors.

Animals↗

PubMed2002

Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles.

BC1 RNA and BC200 RNA are two non-homologous, small non-messenger RNAs (snmRNAs) that were generated, evolutionarily, quite recently by retroposition. This process endowed the RNA polymerase III transcripts with central adenosine-rich regions. Both RNAs are expressed almost exclusively in neurons, where they are transported into dendritic processes as ribonucleoprotein particles (RNPs). Here, we demonstrate with a variety of experimental approaches that poly(A)-binding protein (PABP1), a regulator of translation initiation, binds to both RNAs in vitro and in vivo. We identified the association of PABP with BC200 RNA in a tri-hybrid screen and confirmed this binding in electrophoretic mobility-shift assays and via anti-PABP immunoprecipitation of BC1 and BC200 RNAs from crude extracts, immunodepleted extracts, partially purified RNPs and cells transfected with naked RNA. Furthermore, PABP immunoreactivity was localized to neuronal dendrites. Competition experiments using variants of BC1 and BC200 RNAs demonstrated that the central adenosine-rich region of both RNAs mediates binding to PABP. These findings lend support to the hypothesis that the BC1 and BC200 RNPs are involved in protein translation in neuronal dendrites.

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