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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 29, 2013

 

Motor proteins are known to haul mRNA up and down the cell's cytoskeleton,
which essentially functions as a cell's internal roadway, in order to place mRNA
in the correct position to read a gene and produce a specific protein chain.







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2-way traffic enables proteins to avoid errors

Messenger RNA may move in more than one direction in order to get the job done.

Scientists have found that mRNA may travel one direction, then board another motor protein, and head in the opposite direction to get to the gene on the DNA which it ultimately needs to read in order to generate a protein.

It's a pretty important journey, because mRNA determines which proteins are expressed that determine the identity of a cell — such as differentiating a brain cell from a muscle cell. The research was led by Graydon B. Gonsalvez, PhD, cell biologist at the Medical College of Georgia at Georgia Regents University.

"It used to be thought there was a simple scenario behind cargo movement, a Dynein motor moves in one direction and a Kinesin motor moves in the other direction, thus balancing the polarity mRNA needs to function" said Gonsalvez, corresponding author of the study appearing in the journal PLOS ONE.


Like a motorist on a backed-up interstate, scientists at MCG and the University of Cambridge, have found that mRNA needs flexibility to maneuver around potentially numerous obstacles in its path in order to arrive at the right spot on a gene and begin protein creation.


"The ability of motor proteins to reverse in their tracks is important to their ability to eventually get where they need to go," Gonsalvez said. And location is everything, as mRNAs need to be in a specific location to initiate expression of a specific protein.

While too much misdirection is incompatible with life, a little is OK and maybe even normal. But health consequences of misplaced protein expression can include cancers, multiple sclerosis, Alzheimer's and Fragile X syndrome.


"Most human diseases come from not a loss of a process, but a compromise to that process,"

Graydon B. Gonsalvez, PhD, cell biologist at the Medical College of Georgia at Georgia Regents University


The scientists suspected a bidirectional ability when they saw the two motor proteins, which normally are headed in opposite directions, parked side-by-side within a cell. When researchers removed one idle motor protein allowing it to move in the opposite direction, delivery (or localization), of the cargo mRNA was compromised.

"What we identified is that many things can reverse a track," Gonsalvez said. "If motors only move in one direction, they could become stuck and comprimise protein initiation.

Motor proteins have long been known to haul mRNA up and down the cell's cytoskeleton, which essentially functions as a cell's internal roadway. Gonsalvez recently received a $1.4 million grant from the National Institutes of Health to fill in other important gaps about the mRNA journey — like how do motor proteins identify which mRNA to transport.

Gonsalvez likens the routing system for mRNA to a ZIP code system. Proteins must flag the mRNA for travel. "Something is telling the cell that one mRNA is different from another," he said.

In the case of Fragile X syndrome, for example, Gonsalvez suspects that one or more protein flags that should be stuck onto mRNA are missing so the motors can't tell where the mRNA needs to be moved. Another question Gonsalvez wants to answer is how mRNA holds on for the ride as motor proteins don't bind with it directly.

"These are not easy questions to answer. But we believe once we have the answers, we understand the process. Then we will be able to identify defects in this process and have a disease pathology," adds Gonsalvez.


Gonsalvez notes that transporting mRNA is lifelong, as proteins have a limited life and are constantly being replaced.


His animal research model is the fruit fly as technology is available to selectively knock out motor proteins within specific drosophila cells.

Abstract
In order for eukaryotic cells to function properly, they must establish polarity. The Drosophila oocyte uses mRNA localization to establish polarity and hence provides a genetically tractable model in which to study this process. The spatial restriction of oskar mRNA and its subsequent protein product is necessary for embryonic patterning. The localization of oskar mRNA requires microtubules and microtubule-based motor proteins. Null mutants in Kinesin heavy chain (Khc), the motor subunit of the plus end-directed Kinesin-1, result in oskar mRNA delocalization. Although the majority of oskar particles are non-motile in khc nulls, a small fraction of particles display active motility. Thus, a motor other than Kinesin-1 could conceivably also participate in oskar mRNA localization. Here we show that Dynein heavy chain (Dhc), the motor subunit of the minus end-directed Dynein complex, extensively co-localizes with Khc and oskar mRNA. In addition, immunoprecipitation of the Dynein complex specifically co-precipitated oskar mRNA and Khc. Lastly, germline-specific depletion of Dhc resulted in oskar mRNA and Khc delocalization. Our results therefore suggest that efficient posterior localization of oskar mRNA requires the concerted activities of both Dynein and Kinesin-1.

Authors: Paulomi Sanghavi, Shobha Laxani, Xuan Li, Simon L. Bullock, Graydon B. Gonsalvez Published: Nov 11, 2013DOI: 10.1371/journal.pone.0080605

The published research was funded by the American Cancer Society and the NIH.