An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity

Neuron ◽  
2021 ◽  
Author(s):  
Michael Closser ◽  
Yuchun Guo ◽  
Ping Wang ◽  
Tulsi Patel ◽  
Sumin Jang ◽  
...  
2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.


Genetics ◽  
2020 ◽  
Vol 217 (1) ◽  
Author(s):  
Jaclyn M Noshay ◽  
Alexandre P Marand ◽  
Sarah N Anderson ◽  
Peng Zhou ◽  
Maria Katherine Mejia Guerra ◽  
...  

Abstract Transposable elements (TEs) have the potential to create regulatory variation both through the disruption of existing DNA regulatory elements and through the creation of novel DNA regulatory elements. In a species with a large genome, such as maize, many TEs interspersed with genes create opportunities for significant allelic variation due to TE presence/absence polymorphisms among individuals. We used information on putative regulatory elements in combination with knowledge about TE polymorphisms in maize to identify TE insertions that interrupt existing accessible chromatin regions (ACRs) in B73 as well as examples of polymorphic TEs that contain ACRs among four inbred lines of maize including B73, Mo17, W22, and PH207. The TE insertions in three other assembled maize genomes (Mo17, W22, or PH207) that interrupt ACRs that are present in the B73 genome can trigger changes to the chromatin, suggesting the potential for both genetic and epigenetic influences of these insertions. Nearly 20% of the ACRs located over 2 kb from the nearest gene are located within an annotated TE. These are regions of unmethylated DNA that show evidence for functional importance similar to ACRs that are not present within TEs. Using a large panel of maize genotypes, we tested if there is an association between the presence of TE insertions that interrupt, or carry, an ACR and the expression of nearby genes. While most TE polymorphisms are not associated with expression for nearby genes, the TEs that carry ACRs exhibit enrichment for being associated with higher expression of nearby genes, suggesting that these TEs may contribute novel regulatory elements. These analyses highlight the potential for a subset of TEs to rewire transcriptional responses in eukaryotic genomes.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Audrey Montigny ◽  
Patrizia Tavormina ◽  
Carine Duboe ◽  
Hélène San Clémente ◽  
Marielle Aguilar ◽  
...  

Abstract Background Recent genome-wide studies of many species reveal the existence of a myriad of RNAs differing in size, coding potential and function. Among these are the long non-coding RNAs, some of them producing functional small peptides via the translation of short ORFs. It now appears that any kind of RNA presumably has a potential to encode small peptides. Accordingly, our team recently discovered that plant primary transcripts of microRNAs (pri-miRs) produce small regulatory peptides (miPEPs) involved in auto-regulatory feedback loops enhancing their cognate microRNA expression which in turn controls plant development. Here we investigate whether this regulatory feedback loop is present in Drosophila melanogaster. Results We perform a survey of ribosome profiling data and reveal that many pri-miRNAs exhibit ribosome translation marks. Focusing on miR-8, we show that pri-miR-8 can produce a miPEP-8. Functional assays performed in Drosophila reveal that miPEP-8 affects development when overexpressed or knocked down. Combining genetic and molecular approaches as well as genome-wide transcriptomic analyses, we show that miR-8 expression is independent of miPEP-8 activity and that miPEP-8 acts in parallel to miR-8 to regulate the expression of hundreds of genes. Conclusion Taken together, these results reveal that several Drosophila pri-miRs exhibit translation potential. Contrasting with the mechanism described in plants, these data shed light on the function of yet undescribed primary-microRNA-encoded peptides in Drosophila and their regulatory potential on genome expression.


Author(s):  
Roman Zvarych ◽  
Tetyana Polishchuk

Goal. The purpose of the work is a comprehensive analysis of the main problems of the regulatory potential of legal culture and legal awareness of the individual and its implementation in modern Ukrainian society. Method. The study used a set of theoretical methods of scientific knowledge, in particular: the method of scientific analysis; system-structural; historical and legal; axiological; comparative law; formal-legal and method of generalization. Results. In the course of the research it was proved that the modern philosophy of realization of regulatory potential of legal culture and legal consciousness should consist in strengthening of humanizing character of regulatory influence, be directed not on authoritarian authoritarian, imperative attribution, authorizing, binding types of legal regulations that authoritatively guide the actions, behavior of people and are seen as omnipotent universal mechanisms for solving problems of social life, and to create conditions for the realization of freedom, human potential, its legal status, social activity, creativity and initiative , which, of course, must be implemented on the basis of social, legal and moral norms enshrined in society. Scientific novelty. According to the results of the study, the new conceptual foundations of the regulatory potential of legal culture and legal awareness should be aimed at creating conditions for identifying deep dimensions of the inner world of man, his individual legal worldview, which allows him to become the creator of social and legal reality. Practical significance. The results of the research can be useful in the process of forming a general theoretical concept of the regulatory potential of legal culture and legal consciousness of modern Ukrainian society.


FEBS Letters ◽  
2017 ◽  
Vol 591 (24) ◽  
pp. 3960-3977 ◽  
Author(s):  
Subashika Govindan ◽  
Denis Jabaudon

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ximena Ibarra-Soria ◽  
Thiago S Nakahara ◽  
Jingtao Lilue ◽  
Yue Jiang ◽  
Casey Trimmer ◽  
...  

The mouse olfactory sensory neuron (OSN) repertoire is composed of 10 million cells and each expresses one olfactory receptor (OR) gene from a pool of over 1000. Thus, the nose is sub-stratified into more than a thousand OSN subtypes. Here, we employ and validate an RNA-sequencing-based method to quantify the abundance of all OSN subtypes in parallel, and investigate the genetic and environmental factors that contribute to neuronal diversity. We find that the OSN subtype distribution is stereotyped in genetically identical mice, but varies extensively between different strains. Further, we identify cis-acting genetic variation as the greatest component influencing OSN composition and demonstrate independence from OR function. However, we show that olfactory stimulation with particular odorants results in modulation of dozens of OSN subtypes in a subtle but reproducible, specific and time-dependent manner. Together, these mechanisms generate a highly individualized olfactory sensory system by promoting neuronal diversity.


2019 ◽  
Author(s):  
Austin Q. Seroka ◽  
Chris Q. Doe

AbstractThe generation of neuronal diversity is essential for circuit formation and behavior. Morphological differences in sequentially born neurons could be due to intrinsic molecular identity specified by temporal transcription factors (henceforth called intrinsic temporal identity) or due to changing extrinsic cues. Here we use the Drosophila NB7-1 lineage to address this question. NB7-1 sequentially generates the U1-U5 motor neurons; each has a distinct intrinsic temporal identity due to inheritance of a different temporal transcription factor at time of birth. Here we show that the U1-U5 neurons project axons sequentially, followed by sequential dendrite extension. We misexpress the earliest temporal transcription factor, Hunchback, to create “ectopic” U1 neurons with an early intrinsic temporal identity but later birth-order. These ectopic U1 neurons have axon muscle targeting and dendrite neuropil targeting consistent with U1 intrinsic temporal identity, rather than their time of birth or differentiation. We conclude that intrinsic temporal identity plays a major role in establishing both motor axon muscle targeting and dendritic arbor targeting, which are required for proper motor circuit development.


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