Mini-Reviews, Long Noncoding RNA, and the Bread Used in Sandwiches: Why None of These Should Be Taken for Granted

One of the great functions provided by the journal Cell and other publications  is the witty, quickly- read but nonetheless sense-making mini-review.

 Mini-reviews have been around for seemingly forever but became a scientist’s (or a science librarian’s) best friends on a more regular basis about thirty years ago. Certain classes of journals, particularly Elsevier’s Trends series made them academically respectable. They did this  by attracting as mini-review authors and readers, both seriously well-established scientists and rising stars with serious promise.

The novel idea was that if a mini-review author was skillful enough,  that author could write an easily-read  paper that puts together perhaps half a dozen ideas.

But apart from the mini-review author,  few if any other people had figured out that there were emerging connections and trends in these seemingly disparate ideas.

And the genius of the mini-review was that the author had to  capture interest and equally importantly, make real, if sometimes, unexpected, sense in 3-5 pages.

Min-reviews share some functions along with traditional review articles.

Traditional review articles are also sense-making and also written by invited experts and also integrate sometimes disparate works into a grand unified theme.

But  traditional review articles are usually very long (from 20-100 pages, with anywhere from 50-500 references) and tend to take a magisterial tone.

The difference in experience is that a mini-review is like a comedian with great timing who tells half-a-dozen jokes   riffing on something topical in the course of a few minutes, while a traditional review article  can sometimes be like having your in-laws   read aloud for hours from their inexplicably (to them) as-yet unpublished 1000  page  treatise on humor.

You go to the first  event because you want to, and the second only when you have to.

“The Dark Matter of the Genome”

 

Far more enjoyable on-point intellectual entertainment  is  what you find in  with Nagano & Fraser’s (2011) “Leading Edge Minireview” entitled “No-Nonsense functions for long Noncoding RNAs in the April 15^th, 2011 issue of Cell. 

First, some background for an analogy the mini-review authors use:  “Dark Matter.”

Astrophysicists have long posited that there are  vast areas of space with no bright objects (like stars of galaxies) that are seemingly void.

Yet, because of certain anomalies observed in the behavior of brighter objects,  these areas must contain matter that has a great deal of mass and various unseen, but real powers,  such as gravitational attraction.

Astrophysicists have termed the missing material “Dark Matter.”  They argue that it must be out there, and must be doing something, in part because  of their calculations, but in part also because it simply offends their scientific sensibilities .

For molecular biologists, this “Dark Matter” phrase has been used for some time for  so-called “junk”  DNA and RNA (“junk” because even though there are long stretches of the material, molecular biologists   haven’t been able to figure out what it does, if anything.)

Noncoding RNA is the “Dark Matter” of the genome of most interest lately, because much as astrophysicists would say: it’s out there and must be good for, or must be doing,  something.

Noncoding RNA simply seems always to be  in the cell, but not directly involved in the principle job of RNA: Transcribing the information from DNA to itself, to in turn, make specific proteins that would form up on the RNA and then unzip off that  RNA template  and break off  when the principal building blocks (amino acids, peptides and somewhat larger protein fragments) are  more-or-less fully formed. 

These newly made and subsequently self-assembling proteins would then make up most of the structures,  and often regulate most of  the functions,  of the cell.

Bread & Long Noncoding RNAs

What the authors cited in Nagano and Fraser have begun to comprehend is that researchers have been looking at the structure and function  underlying protein making processes and seeing a kind of sandwich-making process , and have routinely underappreciated that various forms of bread, are more than just “there” while the seemingly  important sandwich fillings get assembled.

Instead, the different forms of bread makes the rest of the sandwich  able to be assembled in the first place, and help it hang together.

At its simplest, bread hold the sandwich together by providing something sturdy on which the generally wetter and more softly textured fillings can be contained or housed until the fillings can be consumed (along with the bread). So, it appears, do seemingly inert noncoding long RNAs. They do this by providing what amounts to weight-bearing scaffolding.  

Entire buildings can get assembled without the scaffolding seeming to be much more than a place where active workers carry out their special functions, yet, it increasingly appears that without that seemingly dumb scaffolding, a lot of buildings could not be built by skilled tradespeople, despite their advanced training and experience.

Likewise with the more sophisticated parts of a sandwich. They can’t get “there” without a “here”  from which to get going.

Consider that one of the functions of bread is also to provide flavor enhancers like condiments a place to meet and meld with one another.  So too can long noncoding RNAs, and do so in two important ways.

In the first sense,  long noncoding RNAs provide nooks and crannies (like the famous Thomas’ English muffins ads)  in which seemingly more active components, like chromatin modifiers, can come together, and influence the assembly of new proteins.

In the second sense, long noncoding RNA can also serve a kind of  dampening down function, much the way that certain intense flavors can be tamed by their being applied to the bread for later more gradual release.

Think of intensely spicy mustard or hot chili sauce. You can’t eat them straight out of the jar or bottle generally, but if placed on bread in a thin layer, they provide enhancement without overpowering. 

Or think of the function of the middle slice of bread or toast in a club sandwich.

 It allows for the flavor and texture of the bacon, lettuce, tomato, and mayo to develop in one layer of the sandwich (which is  on one side of the middle slice), while on the other side of that same middle slice of bread or toast, the turkey  and mayo can make their presence, and weight felt, and actually deliver a lot more nutrition,  without their own  taste and texture being overcome but being instead enhanced that complex, tastier, top layer.  

Similarly, long noncoding RNAs have now been shown to  play a role in some transcription silencing by dampening down  opposing reactions, for a time at least.

Some proteins need to be assembled in spite of others, and without something like long noncoding RNAs that sometimes mask antithetic assembly sites, they don’t get made. Yet when they are finally made, the normal processes of making and releasing the antagonistic proteins can return so that the cell that needs both kinds of proteins gets them when it wants them, in the proportions that work.

 Long noncoding RNAs can also function much like a strip of flat bread as seen as used in a sandwich wrap: They can get around  fillings and  restrain them from falling out,  yet be cut in half, and keep each half’s contents subsequently intact.

Long chain noncoding RNA seems to do this by working with a protein complex called cohesin  to serve together as a wrap  around sister chromosomes ( called chromatids ) during their   duplication in the course of mitosis or meisosis.

They hold the chromatids together until duplicative assembly is completed, and when it is done, they somehow manage to keep the now cut and separating halves from becoming undone.

So what have you learned?

Three things.

Both bread and long noncoding RNAs deserve a lot more respect.

And you might not have appreciated this as much as you do now, owing to an exemplar of a great mini-review, meaning that of Nagano and Fraser.

My little blog was well, like amateur night at a comedy club: You just get up there and do your best.

Tony Stankus, FSLA [email protected]

Editor-in-Chief, Science & Technology Libraries

Life Sciences Librarian, Science Coordinator & Professor

University of Arkansas Libraries MULN 223 E

365 North McIlroy Avenue

Fayetteville AR 72701-4002

 

Hung, Tiffany, and Howard Y. Chang. 2010. Long noncoding RNA in genome regulation: Prospects and mechanisms. RNA Biology 7 (5) (SEP-OCT): 582-5.

Kapranov, Philipp, Georges St Laurent, Tal Raz, Fatih Ozsolak, C. Patrick Reynolds, Poul H. B. Sorensen, Gregory Reaman, et al. 2010. The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA. BMC Biology 8 (DEC 21): 149.

Lickiss, T., T. Sirey, L. Bluy, J. Taylor, and Z. Molnar. 2011. Long noncoding RNA partners of the transcription factor Satb2 in callosal projection neurons of the mouse cerebral cortex. Journal of Anatomy 218 (3) (MAR): 354.

Nagano, Takashi & Peter Fraser. 2011. Non-nonsense functions for long noncoding RNAs. Cell 145:  178-181.

Pasmant, Eric, Audrey Sabbagh, Michel Vidaud, and Ivan Bieche. 2011. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB Journal 25 (2) (FEB): 444-8.

Turner, Anne-Marie W., and Kevin V. Morris. 2010. Controlling transcription with noncoding RNAs in mammalian cells. BioTechniques 48 (6) (JUN): IX,+.

Ulveling, Damien, Claire Francastel, and Florent Hube. 2011. When one is better than two: RNA with dual functions. Biochimie 93 (4) (APR): 633-44.

Wang, Kevin C., Yul W. Yang, Bo Liu, Amartya Sanyal, Ryan Corces-Zimmerman, Yong Chen, Bryan R. Lajoie, et al. 2011. A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature 472 (7341) (APR 7): 120-U158.

Wang, Xiangting, Xiaoyuan Song, Christopher K. Glass, and Michael G. Rosenfeld. 2011. The long arm of long noncoding RNAs: Roles as sensors regulating gene transcriptional programs. Cold Spring Harbor Perspectives in Biology 3 (1) (JAN): a003756.

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