Article: RNA can be heredity molecule

RNA can be heredity molecule
Findings in mice suggest RNA found in human sperm might also affect human
inheritance
By Charles Q. Choi

[Published 25th May 2006 06:34 PM GMT]
RNA in the sperm and eggs of mice can transfer heritable traits, scientists
report in this week's Nature. The findings add another wrinkle to the
current understanding of what drives inheritance, and suggest that RNA found
in human sperm may also influence genetic expression.

"This could add a great possibility for variation into what is already known
about classical genetic variation," study author Minoo Rassoulzadegan at the
University of Nice in France told The Scientist.

The focus of the current study is Kit, a tyrosine kinase receptor critical
to development. The researchers engineered a mutation, tm1Alf, which both
suppressed Kit synthesis and generated lacZ reporter sequences. Homozygote
tm1Alf mice die shortly after birth, while heterozygotes possess white feet
and a white tail tip.

When the researchers interbred heterozygotes, most offspring that did not
possess the mutant tm1Alf allele still maintained the white patches of their
parents. Polymerase chain reaction (PCR) analyses indicated these mice
lacked lacZ sequences, and Southern blot analyses confirmed they had
wild-type genomes. Rassoulzadegan and her colleagues suggested this
phenomenon was similar to paramutation, a heritable epigenetic change
investigated most thoroughly in plants. Paramutated offspring also resulted
when the researchers crossed heterozygotes with wild-type mice, regardless
of the sex combination.

Paramutated mice possessed half the levels of mature Kit mRNAs (similar to
heterozygotes), and Northern analysis showed they also had aberrantly sized
Kit RNA molecules. These different RNA molecules may originate from abnormal
arrest of transcription, abnormal initiation of transcription, or irregular
post-transcriptional processing, Rassoulzadegan told The Scientist.

In normal mice, Kit transcription is restricted to spermatogonia and reduced
or silent from meiosis onward. However, in paramutated and heterozygote
mice, the researchers found significant amounts of Kit RNA in both
spermatids and mature sperm.

To test if RNA caused the paramutation, Rassoulzadegan and her colleagues
injected RNA from heterozygotes into normal wild-type mouse embryos. Close
to half of all resulting mice and their offspring showed the heterozygote
white tail tip signature, suggesting the injected RNA drove the trait. Since
the abnormally sized RNAs linked with the paramutation apparently resulted
from partial degradation of Kit RNAs, the investigators tried an additional
experiment: degrading RNAs in normal wild-type embryos with two Kit-specific
microRNAs (miRNAs). They found that either Kit-specific miRNA, or both,
could result in high frequencies of the white tail phenotype that were
heritable.

Full Text at TheScientist
http://www.the-scientist.com/news/daily/23494/

Posted by
Robert Karl Stonjek


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