Archive for ‘Molecular biology’

December 12, 2011

Long non-coding RNA prevents the death of maturing red blood cells

The main function of RNA was identified early on as being a template – in the form of messenger RNA that reflects the encoding of genes in DNA – for the construction of proteins. A few other forms of RNA were also recognized as playing a well-defined but subsidiary role in this process. However, research within the past five years has established that only 10 to 20% of RNA transcribed from DNA actually serves as a template for proteins.

The function of much of the remaining transcribed RNA is generally unknown. Many of these RNAs are short, with only a few tens of nucleotides, such as microRNA (miRNA). About 1000 different forms of miRNA have beein identified in the human genome, and the effective role of many of these has been discovered.

Longer forms of non-coding RNA, having more that 200 nucleotides, are known simply as long non-coding RNA (lncRNA). Only about 100 have been studied in mammalian tissues so far. The function of only a few of these has been determined. For example, one type is important in regulating stem cells during embryonic development.

Now another lncRNA has been found to play an important role in the maturation of red blood cells.

Long non-coding RNA prevents the death of maturing red blood cells

A long non-coding RNA (lncRNA) regulates programmed cell death during one of the final stages of red blood cell differentiation, according to Whitehead Institute researchers. This is the first time a lncRNA has been found to play a role in red blood cell development and the first time a lncRNA has been shown to affect programmed cell death.

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November 13, 2011

Learning why BRCA1 mutations lead to breast cancer

BRCA1 is a gene whose name is among the most familiar to the general public of all genes – for the unfortunate reason that mutations of BRCA1 are associated with significantly increased hereditary risk for breast cancer (as the name suggests). Strangely, however, it’s still not known exactly how mutations of BRCA1 confer this greater risk for cancer. But recent research has narrowed down the possibilities.

The protein that the gene codes for, BRCA1, is a fairly long chain of 1863 amino acids. BRCA1 is known to be involved in repair of damaged DNA. If BRCA1 is defective (due to a gene mutation), the failure to properly repair DNA (which can become damaged for many possible reasons) can lead to a cell becoming cancerous.

Previous research has identified around 1500 different mutations of BRCA1 associated with cancer risk. But most of these mutations directly affect the amino acids of only two different regions of BRCA1. Every protein has an amine group at one end of its chain and a carboxyl group at the other end. One of the two regions in which mutations lead to cancer is at the amino end and is called the “RING domain”. The other region, near the carboxyl end, is called BRCT (BRCA1 carboxyl-terminal tandem repeats).

The RING domain is known to have a role in the process that attaches a marker called ubiquitin to a protein in order to identify the protein as ready for recycling. The BRCT region is associated with the process of protein phosphorylation, which is a key element of chemical signaling within cells. What hasn’t been known is what aspects of DNA repair are disrupted by defects in one or both of these regions.

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November 9, 2011

Retrotransposons may influence brain activity

Retrotransposons (known informally as “jumping genes”) are like viruses that are permanently encoded in a genome. They are genetic elements that can cause additional copies of themselves to be added to the genome. Because of this ability, they make up a large part of the noncoding (“junk”) DNA in a genome. About 42% of human DNA is active or inactive retrotransposons. In other mammals the percentage may be even higher. Even more of our genomes may represent traces of retrotransposon activity in the distant past.

As far as biologists can tell, retrotransposons generally serve no useful purpose. They exist, like parasites, simply because they can. However, the view that they have no use may need to be revised in light of new research. On the other hand, retrotransposon activity that isn’t adequately suppressed may be responsible for neurological diseases from dementia to Parkinson’s to schizophrenia, and perhaps cancer too.

Determination of whether human retrotransposons are beneficial or detrimental is yet to be made. All that’s now been shown, in the new research, is that retrotransposons are active in brain tissue, especially in parts of the brain responsible for learning and memory – specifically the hippocampus and the caudate nucleus.

“Jumping Genes” May Influence Brain Activity

Mobile DNA molecules that jump from one location in the genome to another may contribute to neurological diseases and could have subtle influences on normal brain function and behavior, according to a study published October 30 in Nature. …

Researchers from the Roslin Institute in Edinburgh, Scotland, have now comprehensively mapped retrotransposon insertion sites in the genomes of normal human brain cells for the first time.

They used state-of-the-art DNA sequencing technology to screen for retrotransposons in tissue samples taken postmortem from three individuals who were healthy when alive and had no neurological disease or signs of abnormality in their brain tissue. Focusing on two brain regions—the hippocampus and caudate nucleus—they identified nearly 25,000 different sites for the three main retrotransposon families.

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November 4, 2011

Cell-Aging Hack Opens Longevity Research Frontier

This is pretty important, even though it’s only a proof of concept – not even a first step to developing a useful therapy for age-related health afflictions. What’s been done is to show that a state (senescence), which old cells reach when they near the limit of their useful lives, is not just a somewhat benign way of stopping the cell from becoming cancerous. Instead, senescent cells that aren’t eliminated naturally (by the immune system or by apoptosis) and remain in the body can degrade the health of the organism. Further, causing such cells to be eliminated is not only possible, but improves the organism’s overall health even though it does not lengthen lifespan. (And even this much has only been demonstrated in genetically altered mice, not humans.)

Cell-Aging Hack Opens Longevity Research Frontier

Research into longevity, that most fundamental and intractable of all human health challenges, moves slowly. It deserves to be described in terms of years, not individual studies. But once in a rare while, a finding has the potential to be a landmark.

Such is the case with a new experiment that flushed old, broken-down cells from the bodies of mice, slowing their descent into the infirmities of age.

The large caveats that inevitably apply to mouse studies still apply here, in spades. But even with those, the findings mark the first time that cellular senescence — its importance debated by biologists for decades — has been experimentally manipulated in an animal, demonstrating a fantastic new tool for studying its role in human aging.

The research involved a series of experiments, and if you’re up on your molecular biology, the details are interesting.

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September 17, 2011

Are genes our destiny? ‘Hidden’ code in DNA evolves more rapidly than genetic code, scientists discover

Molecular biologists have known for some time that the genetic code residing in an organism’s DNA is not the only determinant of the organism’s characteristics (its “phenotype“). Identical twin animals and humans, and clones of plants, have the same DNA as their counterparts – yet they are not identical to each other. Various factors can alter how the same DNA is expressed in corresponding cells of twins and clones. The study of these factors makes up the science of epigenetics.

One of the most important epigenetic mechanisms is DNA methylation, which is a chemical modification to individual DNA nucleotides. It is usually the addition of a methyl group to a cytosine base that is adjacent to a guanine base. In humans up to 90% of cytosine-guanine pairs may be methylated. Methylation usually has the effect of silencing genes if it occurs in a gene’s promoter region.

Methylation patterns can be inherited in successive generations of a plant or animal. However, not too surprisingly, small changes of the pattern can occur, since the normal DNA copying process doesn’t automatically reproduce the methylation. Nevertheless, once a mutation of the pattern has occurred in an egg or sperm cell, it can be passed on to later generations. An obvious question is about how the rate of such epigenetic mutations compares with that of mutations in the DNA itself.

New research has answered that question for Arabidopsis thaliana, a form of cress that is a popular model organism for plant biologists. As it happens, mutations of methylation sites occur a whole lot more often than DNA mutations – about 5 orders of magnitude more often.

Are genes our destiny? ‘Hidden’ code in DNA evolves more rapidly than genetic code, scientists discover

The researchers discovered that as many as a few thousand methylation sites on the plants’ DNA were altered each generation. Although this represents a small proportion of the potentially six million methylation sites estimated to exist on Arabidopsis DNA, it dwarfs the rate of spontaneous change seen at the DNA sequence level by about five orders of magnitude.

This suggests that the epigenetic code of plants – and other organisms, by extension – is far more fluid than their genetic code.

Even more surprising was the extent to which some of these changes turned genes on or off. A number of plant genes that underwent heritable changes in methylation also experienced substantial alterations in their expression – the process by which genes control cellular function through protein production.

Further reading:

Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants

September 17, 2011

Researchers discover a switch that controls stem cell pluripotency

Stem cell scientists are continuing to turn up new information on how embryonic (and other) stem cells work. Embryonic stem cells are pluripotent, meaning they can transform into any other cell type. But what determines when and how this happens? The latest research reveals one particular process, probably out of many.

The FOXP1 gene codes for a transcription factor that regulates the expression of other genes important in embryonic development. As it turns out, very slightly different proteins can be produced from FOXP1, depending on a process, alternative splicing, that affects the derived messenger RNA. In one form of the final transcription factor, genes that maintain pluripotency are expressed: OCT4, NANOG, NR5A2, and GDF3. But in the alternative form, genes are expressed that cause the cell to differentiate into a non-pluripotent cell. The question remains as to what causes splicing to take one path or the other.

Researchers discover a switch that controls stem cell pluripotency

Scientists have found a control switch that regulates stem cell “pluripotency,” the capacity of stem cells to develop into any type of cell in the human body. The discovery reveals that pluripotency is regulated by a single event in a process called alternative splicing.

Alternative splicing allows one gene to generate many different genetic messages and protein products. The researchers found that in genetic messages of a gene called FOXP1, the switch was active in embryonic stem cells but silent in “adult” cells—those that had become the specialized cells that comprise organs and perform functions.

Further reading:

An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming

September 8, 2011

Breast-cancer gene keeps DNA under wraps

The gene in question, BRCA1, is the one which, when mutated, makes women who inherit the mutated form much more susceptible to breast and ovarian cancer. Up till now, a good understanding has been lacking of how the protein produced by unmutated BRCA1 acts as a tumor suppressor.

Breast-cancer gene keeps DNA under wraps – Nature News

The protein encoded by the tumour-suppressor gene BRCA1 may keep breast and ovarian cancer in check by preventing transcription of repetitive DNA sequences, says a study published today in Nature. This explanation brings together many disparate theories about how the gene functions and could also shed light on how other tumour suppressors work.

Since the discovery in the mid-1990s that defects in BRCA1 strongly predispose women to breast and ovarian cancer, researchers have suggested numerous ways in which the protein might stop cells from becoming cancerous. Some have focused on its ability to repair DNA damage, whereas others have studied how it regulates cell-cycle checkpoints, transcription or cell proliferation. But until now, no unifying theory of how these different functions might prevent breast and ovarian cancer has emerged.

Further reading:

Cancer: Let sleeping DNA lie

BRCA1 tumour suppression occurs via heterochromatin-mediated silencing

September 5, 2011

New roles emerge for non-coding RNAs in directing embryonic development

Traditionally, the roles of only a few types of RNA have been understood for the significant part they play in cell biology. The short list includes messenger RNA, transfer RNA, and ribosomal RNA. More recently, other types have been added: mircroRNA, small interfering RNA, and antisense RNA.

But that hardly exhausts the list. A more recently discovered type of RNA is large, intergenic non-coding RNA (lincRNA), a particular subtype of long non-coding RNA. LincRNA are so-named because they are not derived from gene-coding DNA, but instead from stretches of DNA lying between genes. New research suggests that an important function of some lincRNAs is to regulate the development of embryonic stem cells in the earliest stages of embryo develpment.

New roles emerge for non-coding RNAs in directing embryonic development – Broad Institute of MIT and Harvard

Scientists at the Broad Institute of MIT and Harvard have discovered that a mysterious class of large RNAs plays a central role in embryonic development, contrary to the dogma that proteins alone are the master regulators of this process. The research, published online August 28 in the journal Nature, reveals that these RNAs orchestrate the fate of embryonic stem (ES) cells by keeping them in their fledgling state or directing them along the path to cell specialization.

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September 1, 2011

Lizard genome sequence solves a human genetic mystery

Lizard genome sequence solves a human genetic mystery – io9

The interesting finding is that a number of non-coding regions of human DNA correspond to active transposons (“jumping genes”) in the lizard DNA.

Another surprise is that the lizards have essentially the same sex chromosomes as mammals – unlike birds.

320 million years ago, mammals and reptiles reached an evolutionary parting of the ways. We’ve now sequenced a lizard genome for the first time ever, and it’s vastly different from our own…but in a few crucial ways, it’s shockingly similar.