Insights into stem cell regulation, cancer & tissue regeneration

04 Oct 2016

Insights into stem cell regulation, cancer & tissue regeneration

Study in flatworm model provide insights into stem cell regulation, cancer and tissue regeneration

Dr Dasaradhi Palakodeti, Intermediate Fellow

Institute for Stem Cell Biology and Regenerative Medicine, Bangalore

By Anusha Krishnan, Research Communications officer, NCBS, Bangalore

Imagine trying to fly a kite without a tail. It swoops and loops and wiggles and finally crashes down into the ground. A kite without a tail is unstable, but add a tail at the right place, and your kite will fly steady.

Curiously, a similar connection between possessing a tail and being stable exists in molecules within living cells. Messenger molecules called mRNAs that convey instructions from DNA to protein factories for protein synthesis behave somewhat like kites. The messengers require a special tail to stabilise them so that they can function. Variability in the tail – in length or in their position, affects the function of the mRNAs, and hence influences gene expression.

Now, a team of scientists from the Institute for Stem Cell Biology and Regenerative Medicine (inStem) and the National Centre for Biological Sciences (NCBS) have found that many mRNAs – about 40% of the total – in the flatworm Schmidtea mediterranea have alternate forms that vary in the lengths and positions of their tails.
This study on S. mediterranea is the first of its kind in flatworm model systems, which, due to their incredible regeneration abilities, provide insights to stem cell regulation, cancer and tissue regeneration. This study could further our understanding of how varying mRNA tails could control gene expression in the context of regeneration.     

In a typical cell, the expression of a gene encoding for a protein involves two major steps – the coding of a messenger RNA or mRNA from the genetic information in DNA, followed by the translation of the mRNA’s message into protein products at the cell’s protein factories. However, before translation, a process called ‘polyadenylation’ adds tails to mRNAs to stabilise these messengers and influence their function.

The addition of these tails generally happens at specific sites – non-coding parts of mRNAs called 3’-untranslated regions or 3’-UTRs. However, through a phenomenon known as ‘alternative polyadenylation’, these tails can be added on to different sites on the mRNA, affecting its stability and therefore the amount or type of protein product formed.

The work has been a collaborative effort between Dasaradhi Palakodeti’s group at inStem and Aswin Seshasayee from NCBS. Apart from using a host of cutting-edge molecular techniques such as Next Generation Sequencing or NGS, the researchers also had to develop specific bioinformatics tools for analysing large amounts of genomic data.

The current study, which has focused on defining and characterizing a genome-wide database of the 3’- UTRs in S. mediterranea could be a very useful resource for researchers in this field. The tools and methods used in the work have been described in a publication in the journal G3:Genes|Genome|Genetics.

The authors of this paper believe that these tools and methods will lay the foundation for crucial breakthroughs in the flatworm model system and in our understanding of stem cell biology and the process of regeneration.

Read the press release on the NCBS website.

Genome-wide analysis of polyadenylation events in Schmidtea mediterranea. Vairavan Lakshmanan, Dhiru Bansal, Jahnavi Kulkarni, Deepak Poduval, Srikar Krishna, Vidyanand Sasidharan, Praveen Anand, Aswin Seshasayee,and Dasaradhi Palakodeti. G3. Genes I Genomes I Genetics

Image credit : Dr Dasaradhi Palakodeti