論文はざっと見る。最初から細かく読まない！Paper: Not to read everything

（１） Title

(2) Figures & Tables

(3) Legends

(4) 要旨　これは (2)-(3) を見ながら、読む。

なれてくるとタイトルと図で半分以上わかる！

http://www.linguamedica.jp/mita/20030618/knockout/knockout.htm

図の見方

特に　差がないところと差があるところを探す。

( 図は比べるように作ってある）。

Figures:Check the differences

How to get the cloned gene? (How to clone or identify the gene?)

(1) 　 From academic scientist

(2) 　 From company 　

(3) 　 PCR (RT-PCR) 　

(4) 　 From DNA library (Hybridization)

(5) 　 From expression library (Antibody)

(6) 　 From expression library (Protein Activity)

(7) 　Microarray analysis

(8) 　Mutant (Complement or Rescue)

AUF1, a Protein Regulator of mRNA Decay

• A ribonucleoprotein called AUF1 has four isoforms that regulate the expression of proteins by interacting with their mRNAs.

• When all isoforms of AUF1 are knocked out, mice experience accelerated aging, cellular senescence, loss of telomerase, and increased tumorigenesis in a manner similar to telomerase knockout mice.

• The P37 isoform of AUF1 interacts with cell cycle protein mRNAs, while the P42 and P45 isoforms activate telomerase and telomerase RNA transcription.

• Growth factors, proto-oncogenes, and pro-inflammatory cytokines are typically inhibited through the rapid degradation of their mRNA. The group of ribonucleoproteins that conduct this form of gene control are known as AU-Rich Element (ARE) Binding Proteins (AUBPs); they bind to regions in the mRNAs that are enriched for the adenine and uracil nucleotides.

• By differential splicing, a single AUF1 mRNA leads to 4 isoforms of the ribonucleoprotein—P37, P40, P42, and P45. The best studied isoform, P37, is the smallest and leads to rapid decline of inflammatory cytokine mRNAs and some cell cycle regulatory mRNAs, all of which have AREs. P40 may act in a similar manner as P37. P42 and P45 activate the transcription of all components of telomerase, and thus connect pro-inflammatory responses to the activation of DNA repair.

• Like their telomerase deficient counterparts, AUF1 knockout mice display severe aging-related phenotypes, including hunchbacks, reduced subcutaneous fat, and atrophy of reproductive organs. AUF1 deficient mice demonstrated widespread cellular senescence due to an accumulation of mRNAs of proteins that block the cell cycle, such as p16Ink4a, p19ARF, and p21CIP. In the absence of AUF1 these cell cycle checkpoint proteins do not degrade.

http://genecenter.hunter.cuny.edu/index.php/meeting-report/auf1-a-protein-regulator-of-mrna-decay