Laura Maria Moreno León

Medical student

UPB

2013

Molecular biology

Medical student

3° Semester

Teacher

Lina Maria Martinez.

Agosto 26- 2013

Medellin, Colombia

Bibliography

Medical Utility

For many years along with the advance of science

It has tried to find effective treatments and

determinative to ending with many diseases that

afflicting humanity. It is for this reason that

studying gene transcription we can have results

very valuable to meet this great goal.

the definition of Dr. Polychronakos about

transcription is very clear: “ DNA is the blueprint

according to which our body is constructed and

functions. Cells "read" this blueprint by

transcribing the information into RNA, which is

then used as a template to construct proteins --

the body's building blocks. Genes are scanned

based on the association of their RNA with

ribosomes -- particles in which protein synthesis

takes place” This definition helps us understand

that transcription is the first step and one of the

most important for gene expression and along with

this the production of proteins in translation.

Through these studies, we can now better

understand the effect of genetic variants in the

translation of RNA to protein and thus to find an

effective way to develop new treatments for

various diseases.

Moreover the discovery of transcription factor

HLH-30 looks very promising for modern medicine

because this modulate the autophagy. It is

activated under conditions of absence of nutrients,

allowing cells to degrade proteins and organelles

to components that can be reused, so that

autophagy plays an important role in development

and cellular growth. There are also closely related

diseases with defects in autophagy like

neurodegenerative diseases and cancer, so I find

the transcription factor HLH-30 is very important

to increase cellular longevity and correct errors in

the coding of proteins that can cause disease.

Laura Maria Moreno León

Transcription

• COOPER, GM. La celula. Cuarta

edicion. Madrid, Espana. Marban,

2008. 113, 348 p.

•MARTINEZ SANCHES, Lina María.

Biología Molecular. Septima edicion.

Medellin, Colombia. UPB, facultad de

medicina 2012. 89-96 p.

Key protein that modulated organismal

aging identified

Science Daily (Aug. 8, 2013)

Scientists at Sanford-Burnham Medical Research Institute have identified a

key factor that regulates the autophagy process, a kind of cleansing

mechanism for cells in which waste material and cellular debris is gobbled

up to protect cells from damage, and in turn, modulates aging. The

findings, published in Nature Communications today, could lead to the

development of new therapies for age-related disorders that are

characterized by a breakdown in this process. Malene Hansen, Ph.D.,

associate professor in Sanford-Burnham's Del E. Webb Center for

Neuroscience, Aging and Stem Cell Research, and her team as well as

collaborators found a transcription factor -- an on/off switch for genes --

that induces autophagy in animal models, including the nematodeC.

elegans, the primary model organism studied in the Hansen lab. This

transcription factor, called HLH-30, coordinates the autophagy process by

regulating genes with functions in different steps of the process. Two years

ago, researchers discovered a similar transcription factor, or orthologue,

called TFEB that regulates autophagy in mammalian cells.

"HLH-30 is critical to ensure longevity in all of the long-lived C.

elegans strains we tested," says Hansen. "These models require active HLH-

30 to extend lifespan, possibly by inducing autophagy. We found this

activation not only in worm longevity models, but also in dietary-restricted

mice, and we propose the mechanism might be conserved in higher

organisms as well."

HLH-30 is the first transcription factor reported to function in all known

autophagy-dependent longevity paradigms, strengthening the emerging

concept that autophagy can contribute to long lifespan. In a previous

study, Hansen and her colleagues discovered that increased autophagy has

an anti-aging effect, possibly by promoting the activity of an autophagy-

related, fat-digesting enzyme. With these findings, scientists now know a

key component of the regulation of autophagy in aging.

Hansen's team is now working to find therapeutic targets, particularly

upstream kinases, molecules that change protein function, which might

actually phosphorylate the transcription factor to alter its function. "We

already have a clue about the protein TOR, a master regulator that

influences metabolism and aging in many species, but there might be other

kinases that regulate HLH-30 or TFEB activity as well," says lead study

author Louis René Lapierre, Ph.D., a postdoctoral fellow in Hansen's

laboratory, and a recent recipient of a K99/R00 Pathway to Independence

career award from the National Institutes of Health.

Autophagy has become the subject of intense scientific scrutiny over the

past few years, particularly since the process -- or its malfunction -- has

been implicated in many human diseases, including cancer, Alzheimer's, as

well as cardiovascular disease and neurodegenerative disorders. HLH-30

and TFEB may represent attractive targets for the development of new

therapeutic agents against such diseases

Understanding the effects of genes on

Human traits

Science Daily ( July 31, 2013)

Recent technological developments in genomics have revealed a

large number of genetic influences on common complex

diseases, such as diabetes, asthma, cancer or schizophrenia.

However, discovering a genetic variant predisposing to a disease

is only a first step. To apply this knowledge towards prevention

or cure, including tailoring treatment to the patient’s genetic

profile –also know as personalized medicine- we need to know

as personalized medicine- we need to know how this genetic

variant affects health.

In a study published today in Nature communications, Dr.

Constantin Polychronakos from the Research Institute of the

McGill University and The University Centre, and collaborators

from McGill University and The university of Texas, propose a

novel approach for scanning the entire genome that will help us

understand the effect of genes on human traits.

“ This completely new methodology really opens up different

ways of understanding how the genome affects the biology of

the human body,” says Dr. Polychronakos, corresponding author

of the study and Director of the Endocrine Genetics Laboratory

at the Montreal Children’s Hospital and Professor in the

Department of Pediatrics and human Genetics at McGill

University.

DNA is the blueprint according to which our body is constructed

and functions. Cells “read” this blueprint by transcribing the

information into RNA, which is then used as a template to

construct proteins –the body's buildings blocks. Genes are

scanned based on the association of their RNA with ribosome –

particles in which protein synthesis takes place.

“ until now, researchers have been focusing on the effects of

disease- associated genomic variants on DNA-to- RNA

transcription, instead of the challenging question of effects on

RNA to protein translation,” says Dr. Polychronakos. “Thanks to

this methodology, we can now better understand the effects of

genetic variants on translation of RNA to protein – a powerful

way of developing biomarkers for personalized and new

therapies”

IntroductionIn 2006 Roger David Kornberg won the

Nobel Prize in chemistry for describing

the structure of RNA polymerase

enzyme complex, important enzymes

in gene transcription in eukaryotes,

because the DNA used as a template to

synthesize RNA.

As mentioned above transcription is a

very important factor in genetic

expression, because molecules of RNA

are synthesized from molds of DNA and

proteins were synthesized from molds

DNA, in translation. La transcription is

made thanks to enzymes RNA

polymerases.

In this folding we can read about two

current news of how transcription of

DNA to RNA and as the final synthesis

of proteins can be a key factor in the

creation of new treatments definitely

ending with common diseases such as

cancer or diabetes, that although

there is great variety of treatments to

control it, the science can not to find a

cure, until this moment.

.

I find it very interesting and important to know our

genome and to know how it affects the biology of

our body, because we can prevent or to cure

diseases that are common in our environment but

difficult to treat it.

I

I think that autophagy is an important mechanism in cell

growth and development, and discovering of the factor

HLH- 30 that regulates autophagy leads us to a very

important step in finding the formula for ¨eternal youth¨

or at least to be able to cure diseases that only until this

moment it have been controlled.

INTRODUCCION:

In 2006 Roger David Kornberg won the Nobel Prize in

chemistry for describing the structure of RNA

polymerase enzyme complex, important enzymes in

gene transcription in eukaryotes, because the DNA

used as a template to synthesize RNA.

As mentioned above transcription is a very

important factor in genetic expression, because

molecules of RNA are synthesized from molds of DNA

and proteins were synthesized from RNA molds in

translation. La transcription is made thanks to

enzymes arn polymerases.

In this folding we can read about two current

news of how transcription of DNA to RNA and as the

final synthesis of proteins can be a key factor in the

creation of new treatments definitely ending with

common diseases such as cancer or diabetes, that

although there is great variety of treatments to

control it, the science can not to find a cure, until

this moment.

There are three types of RNA

polymerases in eukaryotics. RNA

polymerase I transcribes the

three larger molecules rRNA

(28S, 18S and 5.8S), RNA

polymerase II transcribes protein

coding genes to producer mRNA

and finally RNA polymerase III

transcribes genes encoding tRNA

and 5S rRNA.

The transcription has three

phases: Iniciation,

enlongation and termination

Understanding the effects of

genes on Human traits

Science Daily ( July 31, 2013)

Recent technological developments in genomics have revealed a

large number of genetic influences on common complex diseases,

such as diabetes, asthma, cancer or schizophrenia. However,

discovering a genetic variant predisposing to a disease is only a

first step. To apply this knowledge towards prevention or cure,

including tailoring treatment to the patient’s genetic profile –also

know as personalized medicine- we need to know as personalized

medicine- we need to know how this genetic variant affects

health.

In a study published today in Nature communications, Dr.

Constantin Polychronakos from the Research Institute of the

McGill University and The University Centre, and collaborators

from McGill University and The university of Texas, propose a

novel approach for scanning the entire genome that will help us

understand the effect of genes on human traits.

“ This completely new methodology really opens up different ways

of understanding how the genome affects the biology of the

human body,” says Dr. Polychronakos, corresponding author of the

study and Director of the Endocrine Genetics Laboratory at the

Montreal Children’s Hospital and Professor in the Department of

Pediatrics and human Genetics at McGill University.

DNA is the blueprint according to which our body is constructed

and functions. Cells “read” this blueprint by transcribing the

information into RNA, which is then used as a template to

construct proteins –the body's buildings blocks. Genes are scanned

based on the association of their RNA with ribosome –particles in

which protein synthesis takes place.

“ until now, researchers have been focusing on the effects of

disease- associated genomic variants on DNA-to- RNA

transcription, instead of the challenging question of effects on

RNA to protein translation,” says Dr. Polychronakos. “Thanks to

this methodology, we can now better understand the effects of

genetic variants on translation of RNA to protein – a powerful way

of developing biomarkers for personalized and new therapies”

I find it very interesting and important to know

our genome and to know how it affects the

biology of our body, because we can prevent or

to cure diseases that are common in our

environment but difficult to treat it.

Personalized medicine studies to each individual and

their genetic code to prevent disease or if you already

have a diseases to find the most appropriate

treatment, because it has been found that most

diseases have a great genetic influence, so that gene

transcription plays a role very important because it is

this that is responsible for replicating DNA, with all

the genetic information good or bad that it can carry.

Diabetes, asthma, cancer or schizophrenia are

diseases that they have a genetic influence, it is

transmitted through DNA that parents transmit to

their children.

Some diseases can prevent such as diabetes, but

in most cases, we are destined to suffer it. So if

we want to understand it, we have to study the

transcript of our genes, Maybe the science would

correct these problems and we have a much

healthier life.

Dr. Constantin Polychronakos

proposes a new approach for

scanning the entire genome

that will help us understand

the effect of genes on human

traits.

I find it very interesting and

important to know our genome

and to know how it affects the

biology of our body, because

we can prevent or to cure

diseases that are common in

our environment but difficult

to treat it

Key protein that modulated organismal

aging identified

Science Daily (Aug. 8, 2013)

Scientists at Sanford-Burnham Medical Research Institute have identified a

key factor that regulates the autophagy process, a kind of cleansing

mechanism for cells in which waste material and cellular debris is gobbled

up to protect cells from damage, and in turn, modulates aging. The

findings, published in Nature Communications today, could lead to the

development of new therapies for age-related disorders that are

characterized by a breakdown in this process. Malene Hansen, Ph.D.,

associate professor in Sanford-Burnham's Del E. Webb Center for

Neuroscience, Aging and Stem Cell Research, and her team as well as

collaborators found a transcription factor -- an on/off switch for genes --

that induces autophagy in animal models, including the nematodeC.

elegans, the primary model organism studied in the Hansen lab. This

transcription factor, called HLH-30, coordinates the autophagy process by

regulating genes with functions in different steps of the process. Two years

ago, researchers discovered a similar transcription factor, or orthologue,

called TFEB that regulates autophagy in mammalian cells.

"HLH-30 is critical to ensure longevity in all of the long-lived C.

elegans strains we tested," says Hansen. "These models require active HLH-

30 to extend lifespan, possibly by inducing autophagy. We found this

activation not only in worm longevity models, but also in dietary-restricted

mice, and we propose the mechanism might be conserved in higher

organisms as well."

HLH-30 is the first transcription factor reported to function in all known

autophagy-dependent longevity paradigms, strengthening the emerging

concept that autophagy can contribute to long lifespan. In a previous

study, Hansen and her colleagues discovered that increased autophagy has

an anti-aging effect, possibly by promoting the activity of an autophagy-

related, fat-digesting enzyme. With these findings, scientists now know a

key component of the regulation of autophagy in aging.

Hansen's team is now working to find therapeutic targets, particularly

upstream kinases, molecules that change protein function, which might

actually phosphorylate the transcription factor to alter its function. "We

already have a clue about the protein TOR, a master regulator that

influences metabolism and aging in many species, but there might be other

kinases that regulate HLH-30 or TFEB activity as well," says lead study

author Louis René Lapierre, Ph.D., a postdoctoral fellow in Hansen's

laboratory, and a recent recipient of a K99/R00 Pathway to Independence

career award from the National Institutes of Health.

Autophagy has become the subject of intense scientific scrutiny over the

past few years, particularly since the process -- or its malfunction -- has

been implicated in many human diseases, including cancer, Alzheimer's, as

well as cardiovascular disease and neurodegenerative disorders. HLH-30

and TFEB may represent attractive targets for the development of new

therapeutic agents against such diseases

I

I think that autophagy is an important mechanism in cell

growth and development, and discovering of the factor

HLH- 30 that regulates autophagy leads us to a very

important step in finding the formula for ¨eternal youth¨

or at least to be able to cure diseases that only until this

moment it have been controlled.

Scientists identified a key

factor that regulates the

autophagy process.

Autophagy is a a kind of

cleansing mechanism for

cells in which waste

material and cellular

debris is gobbled up to

protect cells from

damage, and in turn,

modulates aging.

Scientists found in nematodeC. Elegans, that

is a animal model a transcription factor,

called HLH-30, this coordinates the

autophagy process by regulating genes with

functions in different steps of the process.

Being able to controlautophagy with factorHLH-30 is a big stepbecause it is known thatautophagy has an anti-aging effect.

Autophagy´s Malfunctionalso has been implicatedin many human diseases,including cancer,Alzheimer's disease ,cardiovascular disease andneurodegenerativedisorders, so HLH-30 andTFEB may be representattractive targets for thedevelopment of newtherapeutic agents againstthese diseases

This shows the nuclear localization of HLH-

30/TFEB in C. elegans. (Credit: Sanford-

Burnham Medical Research Institute)

I think that autophagy is an important

mechanism in cell growth and

development, and discovering of the

factor HLH- 30 that regulates autophagy

leads us to a very important step in

finding the formula for ¨eternal youth¨

or at least to be able to cure diseases

that only until this moment it have been

controlled.

Medical Utility

For many years along with the advance of science It has tried to find

effective treatments and determinative to ending with many diseases

that afflicting humanity. It is for this reason that studying gene

transcription we can have results very valuable to meet this great

goal.

the definition of Dr. Polychronakos about transcription is very clear: “

DNA is the blueprint according to which our body is constructed and

functions. Cells "read" this blueprint by transcribing the information

into RNA, which is then used as a template to construct proteins -- the

body's building blocks. Genes are scanned based on the association of

their RNA with ribosomes -- particles in which protein synthesis takes

place” This definition helps us understand that transcription is the first

step and one of the most important for gene expression and along with

this the production of proteins in translation. Through these studies,

we can now better understand the effect of genetic variants in the

translation of RNA to protein and thus to find an effective way to

develop new treatments for various diseases.

Moreover the discovery of transcription factor HLH-30 looks very

promising for modern medicine because this modulate the autophagy.

It is activated under conditions of absence of nutrients, allowing cells

to degrade proteins and organelles to components that can be reused,

so that autophagy plays an important role in development and cellular

growth. There are also closely related diseases with defects in

autophagy like neurodegenerative diseases and cancer, so I find the

transcription factor HLH-30 is very important to increase cellular

longevity and correct errors in the coding of proteins that can cause

disease.

It is a medical breakthrough to knowthe genes and their impact on diseasesand their treatments that are verycommon these days in order to providea better solution to patients.

The protein HLH- 30 that modulates autophagy is a great

discovery because with this we can find methods to

intervene directly in autophagy and we could correct

genetic defects and deseases in everybody.

In both news we can see how if we

intervene directly in the transcription

process, we can get excellent results to

treat each patient according to their

needs and it is not as it has been doing

all these years with ineffective treatment

that is applied to anyone regardless of

their genome.

COOPER, GM. La célula. Cuarta edición. Madrid, España. Marban, 2008. 113,348 p.

MARTINEZ SANCHES, Lina María. Biología Molecular. Séptima edición.Medellín, Colombia. UPB, facultad de medicina 2012. 89-96 p.

Key protein that modulated organismal aging identified

Science Daily (Aug. 8, 2013)

Understanding the effects of genes on Human traits

Science Daily ( July 31, 2013).