Transcript 10/9

•Homework #2 is due
10/18
•Bonus #1 is due 10/25
•Weekly quiz online
each Thursday, due
each Tuesday
Fig 8.19
Gene Expression is
controlled at all of these
steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 16.1
C. elegans is commonly used to study development
C. elegans development
C. elegans
mutants with
cells that do not
develop
properly.
Fig 12.25 and
C. elegans
mutants with
cells that do not
develop
properly.
The product of
these genes was
found to be
RNA?
MicroRNAs (miRNA) are ~22nt RNAs
that play important regulatory roles
Cell vol. 116,
281-297 2004
miRNA expressed
How do
microRNAs
control gene
expression?
miRNA
processed to
~22nt RNA
Mature miRNA
A processed mRNA ready for translation:
microRNAs inhibit translation by binding to the 3’ end of mRNA
microRNA bind to 3’-UTR
5’-UTR
3’-UTR
miRNA expressed
the 3’ end
with attached
microRNA
interacts with
the 5’ end,
blocking
translation
miRNA
processed to
~22nt RNA
Mature miRNA
miRNAs can lead to
methylation of DNA that
leads to inhibition of
transcription
microRNAs primarily target gene products that
function during development
Tbl 1
tissue specific
expression of mouse
microRNA
PNAS vol. 101 #1 pg 360-365, 2004
Silencing RNAs (siRNA) are artificially
induced dsRNA
Fig 8.22
siRNA with exact matches
to the target mRNA causes
degradation of the mRNA
Fig 8.21
microRNA
Translation inhibited
siRNA
mRNA degraded
Gene Expression is
controlled at all of these
steps:
•DNA packaging
•Transcription
•RNA processing and
transport
•RNA degradation
•Translation
•Post-translational
Fig 16.1
Phosphorylation and
dephosphorylation of
proteins can change
activity
Fig 9.21
Ubiquitinization targets proteins for degradation
Fig 9.23
All protein interactions in an organism compose the
interactome
Some proteins function in the cytoplasm; others need to be
transported to various organelles.
How can proteins be delivered to
their appropriate destinations?
Protein Destinations: secretion or membrane
• Signal sequences target proteins for secretion
Fig 9.24
Translation of secreted proteins
Translation of membrane bound proteins
Translation of secreted or membrane
bound proteins
This step determines secretion or
membrane bound.
Protein Destinations: nucleus Signal anywhere in protein,
Translation in cytoplasm,
Signal not removed
Protein Destinations: mitochondria or
chloroplast
Signal translated first, Translation in cytoplasm, Signal removed
Protein Destinations: signals in protein
determine destination
Development: differentiating cells to become
an organism
Cells function
differently because
they express
different
genes.
The proper control
of gene expression
is critical for proper
development.
So development in
animals is one way.
Inverse relationship between smoking and
weight: more smoking : less weight
Effect of smoking on
fetal development
and how that can
affect adults
Adults exposed to smoke as fetuses have
higher risk of obesity and heart disease
What is the connection?
Obesity, Diabetes, Heart Disease, High Blood
Pressure, Some Cancers all may have some
origins during fetal development.
Adults metabolism may react to poor nutrition
as fetuses…
Adaptation of Thriftiness
or
Catch Up Growth.
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
20 years later found that these babies had
higher rates of obesity.
Adults metabolism may react to poor nutrition
as fetuses…Adaptation of Thriftiness or Catch
Up Growth.
Study of babies born during Dutch famine of
1944-45…
20 years later found that these babies had
higher rates of obesity.
Precise mechanism is not known
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
For Mom’s who abstained during pregnancy, no
effect on fetus or as adult.
What about smoking?
17,000 births studied and checked
at age 16 and 33.
Fetuses exposed to smoking had increased rate
of obesity and more smoking meant more
obesity.
Smoking during first trimester had same effect
as during whole pregnancy.
What about smoking?
For diabetes more than 10 cigarettes per day
gave a 4 times greater risk of diabetes.
What about smoking?
Risk of high blood pressure also increases with
increased exposure to fetus of smoking during
pregnancy
Why?
Why?
Nicotine can inhibit hunger and increase energy
expenditure.
This can lead to poor fetal nutrition.
Why?
Nicotine causes constriction of blood vessels,
and may limit blood flow to the fetus.
Mammalian
circulation
AAL 38.8
Nicotine causes blood vessels to constrict
Why?
CO in blood decreases delivery of O2 to fetus.
Why?
These are all indirect affects…
Nicotine can inhibit hunger and increase energy
expenditure.
Nicotine causes constriction of blood vessels,
and may limit blood flow to the fetus.
CO in blood decreases delivery of O2 to fetus.
Why?
Nicotine and other toxins in smoke may
directly affect hormones that direct fetal
development.
Hormones are
molecules produced in
one cell and signal
another.
Why?
Nicotine and other toxins in smoke may
directly affect hormones that direct fetal
development.
Including hormones that direct brain
development.
So,
Smoking during pregnancy may have indirect
and/or direct affects on fetal development, and
these affects may manifest themselves in adults.
Correlation of weight and relatedness
Correlation of weight (BMI)
Biological siblings
Parents and children living together
Identical twins reared together
Fraternal twins reared together
Identical twins reared apart
Adopted children and parents
Unrelated children living together
%
34
26
80
43
72
4
1
Nature and Nurture:
Are traits coded for by genes fixed while traits
coded for by the environment are under our
control?
•Homework #2 is due
10/18
•Bonus #1 is due 10/25
•Weekly quiz online
each Thursday, due
each Tuesday
Fig 8.19