Reverse Transcriptase: Mediator of Genomic Plasticity

Brosius, Jürgen; Tiedge, Henri

doi:10.1007/978-1-4613-1407-3_8

Cited by 31 publications

(46 citation statements)

References 223 publications

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“…Given the fact that the BC1 and BC200 genes arose independently in evolution (8,63), the close functional correspondence between the two RNAs was not a priori expected (see Discussion).…”

Section: Resultsmentioning

confidence: 98%

“…The genes encoding BC1 RNA and BC200 RNA have evolved independently from two different progenitors via separate phylogenetic routes (8,63). Despite the fact that they are therefore not orthologs, early speculation raised the possibility that BC1 and BC200 RNAs may be functional analogs (63).…”

Section: Discussionmentioning

confidence: 99%

“…Although proteins function as translational repressors in neurons, the case has been made that genes encoding small npcRNAs evolve at a much higher rate than genes encoding proteins and that as a result, such RNAs are eminently suited to enhance an organism's capability to adapt to changing environments (8,11). We posit that the BC1 and BC200 genes were independently selected because they both encode neuron-specific RNAs that (i) contain codes for their delivery to synapto-dendritic domains and (ii) specifically target eIF4A, uncoupling its helicase and ATPase activities.…”

Section: Discussionmentioning

confidence: 99%

“…These capabilities were obviously important for their functional recruitment and subsequent retention in evolution. Once thus recruited, BC RNAs have become indispensable and have remained highly conserved in their respective lineages, i.e., for at least 55 million years in the case of BC1 RNA and for at least 35 million years in the case of BC200 RNA (8).…”

Section: Discussionmentioning

confidence: 99%

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Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism

Lin¹,

Pestova²,

Hellen³

et al. 2008

Molecular and Cellular Biology

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162

152

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Translational repressors, increasing evidence suggests, participate in the regulation of protein synthesis at the synapse, thus providing a basis for the long-term plastic modulation of synaptic strength. Dendritic BC1 RNA is a non-protein-coding RNA that represses translation at the level of initiation. However, the molecular mechanism of BC1 repression has remained unknown. Here we identify the catalytic activity of eukaryotic initiation factor 4A (eIF4A), an ATP-dependent RNA helicase, as a target of BC1-mediated translational control. BC1 RNA specifically blocks the RNA duplex unwinding activity of eIF4A but, at the same time, stimulates its ATPase activity. BC200 RNA, the primate-specific BC1 counterpart, targets eIF4A activity in identical fashion, as a result decoupling ATP hydrolysis from RNA duplex unwinding. In vivo, BC1 RNA represses translation of a reporter mRNA with 5 secondary structure. The eIF4A mechanism places BC RNAs in a central position to modulate protein synthesis in neurons.Local protein synthesis at the synapse, increasing evidence suggests, is one of the key molecular mechanisms that underlie input-specific modulations of synaptic strength and consequently higher brain functions that rely on such synaptic plasticity. Translational control mechanisms in synapto-dendritic domains are thought to be essential for the long-term spatiotemporal modulation of mosaic local protein repertoires. Such mechanisms are therefore attracting increasing interest among neuroscientists and molecular and cellular biologists (reviewed in references 3, 11, 24, 26, 27, 51, 60, and 67).At the same time, there has been growing awareness of the biological significance of small, functional RNAs in eukaryotic cells in general and in neurons in particular (2, 7, 11). Small, non-protein-coding RNAs (npcRNAs) (also known as untranslated RNAs) (9) may be particularly well suited as posttranscriptional regulators of gene expression that enhance brainenvironment interactions (11). Neuronal BC1 RNA is a small dendritic npcRNA (64) that operates as a translational repressor (30,65,66). BC1 RNA, which is targeted to dendrites (38,39) and is abundant at the synapse (13), represses translation at the level of initiation (65, 66).In eukaryotes, translation initiation proceeds in three stages, each of which is mediated by a number of eukaryotic initiation factors (eIFs) (reviewed in references 25 and 43). An eukaryotic initiation factor 2 (eIF2) ⅐ GTP ⅐ GMet-tRNA i ternary complex first binds to the 40S ribosomal subunit to form a 43S preinitiation complex. This complex is subsequently recruited to the mRNA, typically to the 5Ј cap structure, and scans to the initiator codon to form a 48S initiation complex. In the final step, this complex is joined by the large ribosomal subunit to form an 80S monoribosome complex ready for elongation. It is frequently the second step, recruitment of the 43S complex and 48S complex assembly, that is rate limiting and the target for regulation. This step is mediated by the eIF4 family of facto...

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“…Given the fact that the BC1 and BC200 genes arose independently in evolution (8,63), the close functional correspondence between the two RNAs was not a priori expected (see Discussion).…”

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism

Lin¹,

Pestova²,

Hellen³

et al. 2008

Molecular and Cellular Biology

Self Cite

162

152

View full text Add to dashboard Cite

show abstract

“…As RNA viruses are believed to evolutionarily precede the emergence of DNA viruses [16,17], determining the mechanism responsible for direct recombination between RNA and DNA viruses may help address how genes from the "RNA World" were first incorporated into nascent DNA-based genomes during the putative "Virus World" era, and thus further implicate viruses in the RNA-World to DNA-World transition [17,18,171,172]. In any case, the discovery of the BSL RDHlike virus group extends the modular theory of virus evolution [16,29,173,174] to encompass a much broader range of possibilities than previously thought.…”

Section: Identifying Similar Viruses In Other Environmentsmentioning

confidence: 99%

The Boiling Springs Lake Metavirome: Charting the Viral Sequence-Space of an Extreme Environment Microbial Ecosystem

Diemer¹

2000

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Viruses are the most abundant organisms on Earth, yet their collective evolutionary history, biodiversity and functional capacity is not well understood. Viral metagenomics offers a potential means of establishing a more comprehensive view of virus diversity and evolution, as vast amounts of new sequence data becomes available for comparative analysis.Metagenomic DNA from virus-sized particles (smaller than 0.2 microns in diameter) was isolated from approximately 20 liters of sediment obtained from Boiling Springs Lake (BSL) and sequenced. BSL is a large, acidic hot-spring (with a pH of 2.2, and temperatures ranging from 50°C to 96°C) located in Lassen Volcanic National Park, USA. BSL supports a purely microbial ecosystem comprised largely of Archaea and Bacteria, however, the lower temperature regions permit the growth of acid-and thermotolerant Eukarya. This distinctive feature of the BSL microbial ecosystem ensures that virus types infecting all domains of life will be present. The metagenomic sequence data was used to characterize the types of viruses present within the microbial ecosystem, to ascertain the extent of genetic diversity and novelty comprising the BSL virus assemblage, and to explore the genomic and structural modalities of virus evolution. New sequence data from metagenomic surveys of natural virus assemblages was also used to better characterize and define known virus protein families, as some of the viruses found in the BSL environment represent distant relatives of well-characterized isolates. By comparing viral genes and protein sequences from these highly divergent species, it is possible to better understand the dynamics of adaptation and evolution in the virosphere. Additionally, as structures of virus proteins continue to be experimentally determined by X-ray crystallography and cryo-electron microscopy, a merger of structural and metagenomic sequence data allows the opportunity to observe the structural dynamics underlying virus protein evolution.Capsid (structural) proteins from two distinct Microviridae strains; a globally ubiquitous and highly sequence-diverse virus family, were identified in, and isolated from the BSL metagenomic DNA sample. These BSL capsid protein sequences, along with several other homologous sequences derived from metagenomic surveys and laboratory isolates, were mapped to the solved structure of a closely related capsid protein from the Spiroplasma phage-4 microvirus. Patterns of amino acid sequence conservation, unveiled by structure-based homology modeling analysis, revealed that the iii protein sequences within this family exhibit a remarkable level of plasticity, while remaining structurally and functionally congruent.Lateral gene transfer is thought to have had a significant impact on the genomic evolution and adaptation of virus families. Genomic context analysis was also utilized to identify interviral gene transfer within the BSL virus assemblage. An ostensibly rare interviral gene transfer event, having transpired between single-stranded RNA ...

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Analysis and significance of messenger RNA in human ejaculated spermatozoa

Miller¹

2000

Mol. Reprod. Dev.

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Reverse Transcriptase: Mediator of Genomic Plasticity

Cited by 31 publications

References 223 publications

Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism

Translational Control by a Small RNA: Dendritic BC1 RNA Targets the Eukaryotic Initiation Factor 4A Helicase Mechanism

The Boiling Springs Lake Metavirome: Charting the Viral Sequence-Space of an Extreme Environment Microbial Ecosystem

Analysis and significance of messenger RNA in human ejaculated spermatozoa

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