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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive Nov 7, 2013

 

"Two of the three major processes in eukaryotic gene expression — splicing and translation — are now shown to be catalyzed [initiated] by RNA," says Jonathan Staley, PhD







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Further evidence of RNA origin to modern life

RNA is the key function of spliceosomes, molecular machines that control how genes are expressed — or turned on. The discovery of splicesomes establishes that RNA, not protein, is responsible for catalyzing this fundamental biological process and enriches the theory that life on earth began in a world based solely on RNA.

"Two of the three major processes in eukaryotic gene expression — splicing and translation — are now shown to be catalyzed by RNA," says Jonathan Staley, PhD, associate professor of molecular genetics and cell biology at the University of Chicago, and co-corresponding author on the study. "The eukaryotic gene expression pathway is more of an RNA-based pathway than protein-based."

The scientific report from the University of Chicago appears online in Nature.


For genes to be expressed — or read, DNA must be translated or converted into proteins, structural and functional molecules that catalyze chemical reactions necessary for life.

To do so, genetic information stored in DNA is first copied into strands of messenger RNA (mRNA), which is subsequently used to create proteins.


In eukaryotes, almost all genes undergo alternative splicing, in which a precursor form of mRNA is cut and re-stitched together in numerous differing combinations. This significantly increases the number of proteins a single gene will code, and could explain much of the complexity in higher-order organisms. Splicing is a critical biological mechanism — at least 15 percent of all human diseases are due to splicing errors.


Spliceosomes, made from proteins and short, noncoding RNA fragments, splice via catalysis — a biological process usually attributed to protein-based enzymes. However, previous research hints that RNA in the spliceosome might be responsible.

Despite decades of study, this question remained unanswered.


To address this question, Staley and Joseph Piccirilli, PhD, professor of biochemistry, molecular biology and chemistry at the University of Chicago, partnered with graduate students Sebastian Fica and Nicole Tuttle, co-lead authors on the study.

They first disabled the ability of spliceosomes to self-correct errors in splicing. They then modified single atoms on mRNA precursors known to be cut during splicing, as well as several on U6, an RNA subunit of the spliceosome hypothesized to be important for catalysis.

Some of these modifications render splicing ineffective. The scientists systematically rescued this loss-of function, and along the way, investigated sites individually and in combination thus locating areas critical to splicing function, and identifying connections between U6 and mRNA precursors.

The team found that the U6 RNA subunit directly controls catalytic function — effectively acting as the blade of the spliceosome. This is the first experimental proof that RNA is the key functional component of this critical biological mechanism.

They also found remarkable similarities in structure and function between spliceosome RNAs and group II introns, an evolutionarily-ancient class of self-splicing, catalytic RNA found in all major branches of life. They believe this indicates that these two RNA-based splicing catalysts share a common evolutionary origin, providing further evidence that key modern RNA-protein complexes, including the spliceosome and the ribosome, evolved from an RNA world.


"In modern life, protein enzymes catalyze [initiate] most biological reactions. The finding that a system like the spliceosome, which contains more protein than RNA, uses RNA for catalysis and has a molecular ancestor composed entirely of RNA suggests that the spliceosome's reaction center may be a molecular fossil from the 'RNA World.'"

Joseph Piccirilli, PhD, professor, biochemistry, molecular biology and chemistry. University of Chicago


Abstract
In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group II intron RNAs, the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.

The study, "RNA catalyses nuclear pre-mRNA splicing," was supported by the Chicago Biomedical Consortium, with support from the Searle Funds at The Chicago Community Trust, and the National Institutes of Health (R01GM088656). Additional authors include Thaddeus Novak, Nan-Sheng Li, Jun Lu, Prakash Koodathingal and Qing Dai.

Original press release: http://www.eurekalert.org/pub_releases/2013-11/uocm-rcs110413.php