Retrotransposons are "copy-and-paste" insertional mutagens that substantially contribute to mammalian genome content. Retrotransposons often carry long terminal repeats (LTRs) for retrovirus-like ...reverse transcription and integration into the genome. We report an extraordinary impact of a group of LTRs from the mammalian endogenous retrovirus-related ERVL retrotransposon class on gene expression in the germline and beyond. In mouse, we identified more than 800 LTRs from ORR1, MT, MT2, and MLT families, which resemble mobile gene-remodeling platforms that supply promoters and first exons. The LTR-mediated gene remodeling also extends to hamster, human, and bovine oocytes. The LTRs function in a stage-specific manner during the oocyte-to-embryo transition by activating transcription, altering protein-coding sequences, producing noncoding RNAs, and even supporting evolution of new protein-coding genes. These functions result, for example, in recycling processed pseudogenes into mRNAs or lncRNAs with regulatory roles. The functional potential of the studied LTRs is even higher, because we show that dormant LTR promoter activity can rescue loss of an essential upstream promoter. We also report a novel protein-coding gene evolution-
-in which an MT LTR provided a promoter and the 5' exon with a functional start codon while the bulk of the protein-coding sequence evolved through a CAG repeat expansion. Altogether, ERVL LTRs provide molecular mechanisms for stochastically scanning, rewiring, and recycling genetic information on an extraordinary scale. ERVL LTRs thus offer means for a comprehensive survey of the genome's expression potential, tightly intertwining with gene expression and evolution in the germline.
Germline genome defense evolves to recognize and suppress retrotransposons. One of defensive mechanisms is the PIWI-associated RNA (piRNA) pathway, which employs small RNAs for sequence-specific ...repression. The loss of the piRNA pathway in mice causes male sterility while females remain fertile. Unlike spermatogenic cells, mouse oocytes posses also RNA interference (RNAi), another small RNA pathway capable of retrotransposon suppression. To examine whether RNAi compensates the loss of the piRNA pathway, we produced a new RNAi pathway mutant DicerSOM and crossed it with a catalytically-dead mutant of Mili, an essential piRNA gene. Normal follicular and oocyte development in double mutants showed that RNAi does not suppress a strong ovarian piRNA knock-out phenotype. However, we observed redundant and non-redundant targeting of specific retrotransposon families illustrating stochasticity of recognition and targeting of invading retrotransposons. Intracisternal A Particle retrotransposon was mainly targeted by the piRNA pathway, MaLR and RLTR10 retrotransposons were targeted mainly by RNAi. Double mutants showed accumulations of LINE-1 retrotransposon transcripts. However, we did not find strong evidence for transcriptional activation and mobilization of retrotransposition competent LINE-1 elements suggesting that while both defense pathways are simultaneously expendable for ovarian oocyte development, yet another transcriptional silencing mechanism prevents mobilization of LINE-1 elements.
Genes, principal units of genetic information, vary in complexity and evolutionary history. Less-complex genes (e.g., long non-coding RNA (lncRNA) expressing genes) readily emerge de novo from ...non-genic sequences and have high evolutionary turnover. Genesis of a gene may be facilitated by adoption of functional genic sequences from retrotransposon insertions. However, protein-coding sequences in extant genomes rarely lack any connection to an ancestral protein-coding sequence.
We describe remarkable evolution of the murine gene D6Ertd527e and its orthologs in the rodent Muroidea superfamily. The D6Ertd527e emerged in a common ancestor of mice and hamsters most likely as a lncRNA-expressing gene. A major contributing factor was a long terminal repeat (LTR) retrotransposon insertion carrying an oocyte-specific promoter and a 5' terminal exon of the gene. The gene survived as an oocyte-specific lncRNA in several extant rodents while in some others the gene or its expression were lost. In the ancestral lineage of Mus musculus, the gene acquired protein-coding capacity where the bulk of the coding sequence formed through CAG (AGC) trinucleotide repeat expansion and duplications. These events generated a cytoplasmic serine-rich maternal protein. Knock-out of D6Ertd527e in mice has a small but detectable effect on fertility and the maternal transcriptome.
While this evolving gene is not showing a clear function in laboratory mice, its documented evolutionary history in Muroidea during the last ~ 40 million years provides a textbook example of how a several common mutation events can support de novo gene formation, evolution of protein-coding capacity, as well as gene's demise.
Abstract
Tens of thousands of rapidly evolving long non-coding RNA (lncRNA) genes have been identified, but functions were assigned to relatively few of them. The lncRNA contribution to the mouse ...oocyte physiology remains unknown. We report the evolutionary history and functional analysis of Sirena1, the most expressed lncRNA and the 10th most abundant poly(A) transcript in mouse oocytes. Sirena1 appeared in the common ancestor of mouse and rat and became engaged in two different post-transcriptional regulations. First, antisense oriented Elob pseudogene insertion into Sirena1 exon 1 is a source of small RNAs targeting Elob mRNA via RNA interference. Second, Sirena1 evolved functional cytoplasmic polyadenylation elements, an unexpected feature borrowed from translation control of specific maternal mRNAs. Sirena1 knock-out does not affect fertility, but causes minor dysregulation of the maternal transcriptome. This includes increased levels of Elob and mitochondrial mRNAs. Mitochondria in Sirena1−/− oocytes disperse from the perinuclear compartment, but do not change in number or ultrastructure. Taken together, Sirena1 contributes to RNA interference and mitochondrial aggregation in mouse oocytes. Sirena1 exemplifies how lncRNAs stochastically engage or even repurpose molecular mechanisms during evolution. Simultaneously, Sirena1 expression levels and unique functional features contrast with the lack of functional importance assessed under laboratory conditions.
Cilj. Cilj je rada široj AKM zajednici predstaviti javno dostupne alate geokodiranja koji mogu biti korisni za predstavljanje raznolikih zbirki vezanih za pojedino područje. Rad će predstaviti neke ...od javno dostupnih alata te iznijeti njihove prednosti i nedostatke, mogućnosti primjene i pristupačnost.
Pristup/metodologija/dizajn. Teorijski su razgraničeni osnovni pojmovi s kojima se autori virtualnih izložbi i interaktivnih karata susreću (GIS, mapiranje, geokodiranje, geolociranje). Uz pomoć analize koja razmatra prednosti, nedostatke, ustanove kojima je namijenjen te cijenu, napravljena je usporedba sedamnaest javno dostupnih alata za geokodiranje.
Rezultati. Analizirano je 17 alata za geokodiranje. Od 17 promatranih alata, njih 10 ima širok spektar primjene koji, po mišljenju autora, uključuje i AKM zajednicu. Rezultati donose prednosti, nedostatke, cijenu i namjenu (odnosno korisnike) promatranih alata, a proučene su mogućnosti primjene, jednostavnost korisničkog sučelja, otvorenost koda, preglednost, trajnost pristupa i cjenovni rangovi.
Ograničenja. Velik broj javno dostupnih alata za geokodiranje kao i njihov kontinuirani razvoj onemogućuju nam analizu svih. Također, usprkos podrobnom upoznavanju, svi analizirani alati za geokodiranje nisu korišteni od strane autora, samo pojedini, što ostavlja mogućnost da su se pojedine prednosti ili nedostaci previdjeli.
Praktična primjena. U radu su predstavljeni javno dostupni alati za geokodiranja koji mogu biti korisni za promociju digitalnih zbirki na interaktivan i popularan način.
Originalnost/vrijednost. Vrijednost ovoga rada ogleda se u činjenici da su na jednom mjestu obuhvaćeni i analizirani javno dostupni alati za geokodiranje koji mogu poslužiti ustanovama AKM zajednice za njihovu usporedbu prije odlučivanja o odabiru alata za izradu interaktivne karte na temelju vlastitih digitalnih zbirki.
Role of Cnot6l in maternal mRNA turnover Horvat, Filip; Fulka, Helena; Jankele, Radek ...
Life science alliance,
08/2018, Letnik:
1, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Removal of poly(A) tail is an important mechanism controlling eukaryotic mRNA turnover. The major eukaryotic deadenylase complex CCR4-NOT contains two deadenylase components, CCR4 and CAF1, for which ...mammalian CCR4 is encoded by
or
paralogs. We show that
apparently supplies the majority of CCR4 in the maternal CCR4-NOT in mouse, hamster, and bovine oocytes. Deletion of
yielded viable mice, but
females exhibited ∼40% smaller litter size. The main onset of the phenotype was post-zygotic: fertilized
eggs developed slower and arrested more frequently than
eggs, suggesting that maternal CNOT6L is necessary for accurate oocyte-to-embryo transition. Transcriptome analysis revealed major transcriptome changes in
ovulated eggs and one-cell zygotes. In contrast, minimal transcriptome changes in preovulatory
oocytes were consistent with reported
mRNA dormancy. A minimal overlap between transcripts sensitive to decapping inhibition and
loss suggests that decapping and CNOT6L-mediated deadenylation selectively target distinct subsets of mRNAs during oocyte-to-embryo transition in mouse.
Cilj. Cilj je rada prikazati razvoj patentnih citatnih analiza i predstaviti mogućnosti njihove primjene u evaluaciji sveučilišta uz bibliometrijske analize.
Pristup/metodologija/dizajn. Prikazan je ...povijesni razvoj i primjena patentnih citatnih analiza. U drugom dijelu rada izvršena je usporedba hrvatskih, regionalnih i vodećih EU-sveučilišta prema prosjeku patentnih citata na 1000 radova i prosječnoj citiranosti po radu. Za analizu je korišten Scopusov bibliometrijski alat SciVal.
Rezultati. Rad prikazuje primjere citatnih analiza pomoću kojih se uspoređuje patentna citiranost hrvatskih sveučilišta sa sveučilištima u regiji i vodećim sveučilištima iz Europske Unije. Rad analizira patentnu citiranost najvećih hrvatskih sveučilišta: Sveučilišta u Zagrebu, Sveučilišta u Splitu, Sveučilišta u Rijeci i Sveučilišta u Osijeku, kao i patentnu citiranost navedenih sveučilišta prema različitim područjima znanosti. Istražena je citiranost radova pojedinih hrvatskih sveučilišta citiranih u patentima, kao i omjer međunarodne suradnje u radovima citiranim u patentima prema ostalim citiranim radovima promatranih hrvatskih sveučilišta.
Ograničenja. Ograničenje je nedostatak postojećih istraživanja patentnih pokazatelja u Hrvatskoj. Iako patentni citati ukazuju na povezanost sveučilišta i industrijskog sektora, za dubinsku analizu transfera znanja i tehnologije potrebno je koristiti i dodatne indikatore kao što su broj ugovora koje sveučilišta imaju s industrijom, broj konferencija u suradnji s industrijom, broj licenci, spin-off Tvrtki sveučilišta i sl.
Originalnost/vrijednost. Upravo zbog nedostatka relevantne suvremene literature, kao i izvorno hrvatskih radova s ovom temom, smatramo da je važno osvijestiti ulogu kako citatnih analiza tako i patenta, kao i patentometrije u evaluaciji sveučilišta i njihovom daljnjem razvoju, kao i napredovanju sveučilišnog kadra.
miRNAs, ~22nt small RNAs associated with Argonaute (AGO) proteins, are important negative regulators of gene expression in mammalian cells. However, mammalian maternal miRNAs show negligible ...repressive activity and the miRNA pathway is dispensable for oocytes and maternal‐to‐zygotic transition. The stoichiometric hypothesis proposed that this is caused by dilution of maternal miRNAs during oocyte growth. As the dilution affects miRNAs but not mRNAs, it creates unfavorable miRNA:mRNA stoichiometry for efficient repression of cognate mRNAs. Here, we report that porcine ssc‐miR‐205 and bovine bta‐miR‐10b are exceptional miRNAs, which resist the diluting effect of oocyte growth and can efficiently suppress gene expression. Additional analysis of ssc‐miR‐205 shows that it has higher stability, reduces expression of endogenous targets, and contributes to the porcine oocyte‐to‐embryo transition. Consistent with the stoichiometric hypothesis, our results show that the endogenous miRNA pathway in mammalian oocytes is intact and that maternal miRNAs can efficiently suppress gene expression when a favorable miRNA:mRNA stoichiometry is established.
Synopsis
MicroRNAs in mammalian oocytes were thought to be inactive due to their low abundance. This work shows that unique exceptionally abundant miRNAs not only exist but also efficiently repress their targets in mammalian oocytes.
ssc‐miR‐205 and bta‐miR‐10b accumulate to high numbers and are active in oocytes.
The stability of ssc‐miR‐205 likely contributes to its accumulation.
ssc‐miR‐205 suppresses endogenous targets, and contributes to the oocyte‐to‐embryo transition.
MicroRNAs in mammalian oocytes were thought to be inactive due to their low abundance. This work shows that unique exceptionally abundant miRNAs not only exist but also efficiently repress their targets in mammalian oocytes.
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